Laser-induced fluid filled balloon catheter

ABSTRACT

The present disclosure relates generally to the use of medical devices for the treatment of vascular conditions. In particular, the present disclosure provides devices and methods for using laser-induced pressure waves to disrupt vascular occlusions. The present disclosure not only provides devices and methods for using laser-induced pressure waves to disrupt vascular occlusions or portions thereof, but the present disclosure also provides devices and methods for disrupting calcium in the media and/or intima layer of an arterial wall.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation-in-part of commonly assigned,co-pending U.S. application Ser. No. 14/984,050, filed on Dec. 30, 2015which is hereby incorporated herein by reference in its entirety for allthat it teaches and for all purposes, which is a continuation-in-part ofcommonly assigned, co-pending U.S. application Ser. No. 13/800,214,filed on Mar. 13, 2013, now U.S. Pat. No. 9,320,530, which is herebyincorporated herein by reference in its entirety for all that it teachesand for all purposes. U.S. application Ser. No. 14/984,050 claims thebenefit of and priority, under 35 U.S.C. §119(e), to commonly assigned,U.S. Application Ser. No. 62/098,242, filed on Dec. 30, 2014 which ishereby incorporated herein by reference in its entirety for all that itteaches and for all purposes. U.S. application Ser. No. 14/984,050 thebenefit of and priority, under 35 U.S.C. §119(e), to commonly assigned,U.S. Application Ser. No. 62/209,691, filed on Aug. 25, 2015 which ishereby incorporated herein by reference in its entirety for all that itteaches and for all purposes. U.S. application Ser. No. 14/984,050claims the benefit of and priority, under 35 U.S.C. §119(e), to commonlyassigned, U.S. Application Ser. No. 62/232,318, filed on Sep. 24, 2015which is hereby incorporated herein by reference in its entirety for allthat it teaches and for all purposes. U.S. application Ser. No.14/984,050 claims the benefit of and priority, under 35 U.S.C. §119(e),to commonly assigned, U.S. Application Ser. No. 62/248,875, filed onOct. 30, 2015 which is hereby incorporated herein by reference in itsentirety for all that it teaches and for all purposes. U.S. applicationSer. No. 14/984,050 claims the benefit of and priority, under 35 U.S.C.§119(e), to commonly assigned, U.S. Application Ser. No. 62/248,913,filed on Oct. 30, 2015 which is hereby incorporated herein by referencein its entirety for all that it teaches and for all purposes. U.S.application Ser. No. 14/984,050 claims the benefit of and priority,under 35 U.S.C. §119(e), to commonly assigned, U.S. Application Ser. No.62/257,404, filed on Nov. 19, 2015 which is hereby incorporated hereinby reference in its entirety for all that it teaches and for allpurposes. U.S. application Ser. No. 14/984,050 claims the benefit of andpriority, under 35 U.S.C. §119(e), to commonly assigned, U.S.Application Ser. No. 62/261,085, filed on Nov. 30, 2015 which is herebyincorporated herein by reference in its entirety for all that it teachesand for all purposes. The present application claims the benefit of andpriority, under 35 U.S.C. §119(e), to commonly assigned, U.S.Application Ser. No. 62/316,423, filed on Mar. 31, 2016 which is herebyincorporated herein by reference in its entirety for all that it teachesand for all purposes.

FIELD

The present disclosure relates generally to the use of medical devicesfor the treatment of vascular conditions. In particular, the presentdisclosure provides materials and methods for using laser-inducedpressure waves to disrupt vascular blockages and to deliver therapeuticagents to the blockage area.

BACKGROUND

Coronary artery disease (CAD) is the most common form of heart disease,affecting millions of people. Peripheral artery disease (PAD) alsoaffects millions of people. CAD and PAD most often results from acondition known as atherosclerosis, which generally manifests as theaccumulation of a waxy substance on the inside of a subject's arteries.This substance, called plaque, is made of cholesterol, fatty compounds,calcium, and a blood-clotting material called fibrin.

As the plaque builds up, the coronary and peripheral arteries narrows,or becomes stenotic, making it more difficult for blood to flow to theheart. As the blockage worsens in a person's coronary arteries, bloodflow to the heart slows, and a condition called angina pectoris, orsimply angina, may develop. Angina is like a squeezing, suffocating, orburning feeling in the chest. The pain typically develops when the heartrequires additional blood, such as during exercise or times of emotionalstress. In time, a narrowed or blocked artery can lead to a heartattack.

A number of medicines can be used to relieve the angina pain that comeswith CAD, but these medicines cannot clear blocked arteries. A moderateto severely narrowed coronary artery may need more aggressive treatmentto reduce the risk of a heart attack. Similarly, as the plaque builds upin peripheral arteries, the artery narrows, or becomes stenotic, therebymaking it more difficult for blood to flow through the peripheralarteries. The reduced blood flow in the peripheral arteries limits theamount of oxygen that is delivered to the extremities, which in turn maycause pain in the extremities and, in severe cases, gangrene, which mayultimately require amputation.

Balloon angioplasty and other transluminal medical treatments arewell-known and have been proven efficacious in the treatment of stenoticlesions at the core of CAD and/or PAD. In a typical angioplastyprocedure, a catheter is inserted into the groin or arm of a subject andguided to the affected arteries, such as the aorta and into the coronaryarteries of the heart when treating CAD and the peripheral arteries whentreating PAD. There, blocked arteries can be opened with a balloonpositioned at the tip of the catheter.

Initially, angioplasty was performed only with balloon catheters, buttechnical advances have been made and improved patient outcomes havebeen achieved with the placement of small metallic spring-like devicescalled “stents” at the site of the blockage. The implanted stent servesas a scaffold that keeps the artery open. Angioplasty and stentingtechniques are widely used around the world and provide an alternativeoption to bypass surgery for improving blood flow to the heart muscle.There are, however, limitations associated with angioplasty andstenting, one of which is called “restenosis.”

Restenosis occurs when the treated vessel becomes blocked again. Forexample, when a stent is placed in a blood vessel, new tissue growsinside the stent, covering the struts of the stent. Initially, this newtissue consists of healthy cells from the lining of the arterial wall(such as, endothelium). This is a favorable effect because developmentof normal lining over the stent allows blood to flow smoothly over thestented area without clotting. Later, scar tissue may form underneaththe new healthy lining. However, in about 25 percent of patients, thegrowth of scar tissue underneath the lining of the artery may be sothick that it can obstruct the blood flow and produce another blockage.“In-stent” restenosis is typically seen 3 to 6 months after the initialprocedure. Another significant limitation of the use of stents is stentthrombosis, which, although rare (occurring in only 1 percent ofpatients), most commonly presents as acute myocardial infarction.

In addition to angioplasty and the deployment of stents, other types ofintervention for stenotic vessels include atherectomy, bypass surgery,and the use of laser ablation and mechanical cutting systems to reducethe plaque size. Treatments using various pharmacological agents havealso been developed, including medical infusions, drug-eluding stents(DES), and drug eluting balloons (DEB). Given the persistence of CAD andPAD, however, the most efficacious means for improving therapeuticoutcomes may involve combinations of therapies designed not only toreduce plaque size in the short term, but also to prevent futurecomplications such as restenosis. Combinatorial therapies may offer thebest chance to improve therapeutic outcomes for people suffering fromCAD and PAD.

SUMMARY

These and other needs are addressed by the various aspects, embodiments,and configurations of the present disclosure.

The present disclosure provides a catheter comprising of a lumen, aproximal end and a distal end, one or more emitters circumferentiallyarranged around or adjacent to the lumen, a balloon circumferentiallyarranged around a portion of the catheter, at least one energy sourcecoupled to the at least one emitter, wherein said emitter is coupled tothe catheter and disposed within the balloon, wherein said emitter isdisposed proximate to the distal end of the catheter, wherein one ormore liquid medium ports disposed about the catheter and within theballoon, wherein said liquid medium ports are used to fill the balloonwith a liquid medium.

A catheter according to paragraph [0011], wherein the at least oneemitter is configured to emit laser light energy at wavelengths betweenabout 300 nanometers to about 350 nanometers, at pulse durations betweenabout 100 nanoseconds to about 150 nanoseconds, and at frequenciesbetween about 1 pulse per second to about 250 pulses per second.

A catheter according to any of paragraphs [0011]-[0012], wherein the atleast one emitter is configured to emit laser light energy atwavelengths of about 308 nanometers, at pulse durations between about120 nanoseconds and about 140 nanoseconds, and at frequencies betweenabout 25 pulses per second to about 80 pulses per second.

A catheter according to any of paragraphs [0011]-[0013], wherein thetotal energy output for the at least one emitter is between about 30 toabout 80 millijoules per millimeter squared (mJ/mm²).

A catheter according to any of paragraphs [0011]-[0014], wherein thetotal energy output for the at least one emitter may be between about 20to about 1000 millijoules per millimeter squared (mJ/mm²).

A catheter according to any of paragraphs [0011]-[0015] furthercomprising additional emitters within the catheter, the additionalemitters having a distal end corresponding to the distal end of thecatheter, the distal end of the additional emitters being disposeddistally of the balloon catheter.

A catheter according to any of paragraphs [0011]-[0016], wherein thedistal end of the additional emitters are configured to emit laser lightenergy at wavelengths between about 300 nanometers to about 350nanometers, at pulse durations between about 100 nanoseconds to about150 nanoseconds, and at frequencies between about 1 pulse per second toabout 250 pulses per second.

A catheter according to any of paragraphs [0011]-[0017], wherein thedistal end of the additional emitters are configured to emit laser lightenergy at wavelengths of about 308 nanometers, at pulse durationsbetween about 120 nanoseconds and about 140 nanoseconds, and atfrequencies between about 25 pulses per second to about 80 pulses persecond.

A catheter according to any of paragraphs [0011]-[0018], wherein theliquid medium is contrast medium or contrast solution.

A catheter according to any of paragraphs [0011]-[0019], wherein theliquid medium is any one of iodine-containing contrast medium orgadolinium contrast medium.

A catheter according to any of paragraphs [0011]-[0020], wherein theliquid medium is configured to exhibit high absorption of light energyemitted from the at least one emitter at wavelengths of between about 1nanometer to about 1 millimeter, at pulse durations between about 1nanosecond to about 1 second, and at frequencies between about 1 pulseper second to about 1000 pulses per second.

A catheter according to any of paragraphs [0011]-[0021], wherein theliquid medium is delivered into the balloon to create a pressure greaterthan 0.0 atmospheres to about 20.0 atmospheres within the ballooncatheter.

A catheter according to any of paragraphs [0011]-[0022], wherein the atleast one emitter is two or more concentric emitters.

A catheter according to any of paragraphs [0011]-[0023], wherein the atleast one emitter is two or more single emitters.

A catheter according to any of paragraphs [0011]-[0024], wherein the atleast one emitter is configured to translate within the ballooncatheter.

The present disclosure provides a method for treating an obstruction orrestriction within the vasculature of a subject, the method comprisingpositioning a catheter within the vasculature of a subject, the cathetercomprising a lumen, a proximal end and a distal end, one or moreemitters circumferentially arranged around or adjacent to the lumen, aballoon circumferentially arranged around a portion of the catheter, atleast one energy source coupled to the at least one emitter, whereinsaid emitter is coupled to the catheter and disposed within the balloon,wherein said emitter is disposed proximate to the distal end of thecatheter, wherein one or more liquid medium ports disposed about thecatheter and within the balloon, wherein said liquid medium ports areused to fill the balloon with a liquid medium, positioning the balloonadjacent to an obstruction or restriction within the vasculature,inflating the balloon by delivering a liquid medium through an innerlumen of the catheter and out one or more liquid medium ports into theballoon until a desired inflation pressure is obtained, and activatingthe at least one energy source to emit one or more pulses of lightenergy from the at least one emitter within the balloon, whereinemitting the one or more pulses of light energy from the at least oneemitter reacts with the liquid medium and generates a plurality ofpropagating laser-induced pressure waves that engage and disrupt atleast a portion of the vascular obstruction or restriction.

A method according to paragraph [0026], wherein the at least one emitteris configured to emit light energy at wavelengths of between about 300nanometers to about 350 nanometers, at pulse durations between about 100nanoseconds to about 150 nanoseconds, and at frequencies between about 1pulse per second to about 250 pulses per second.

A method according to any of paragraphs [0026]-[0027], wherein the atleast one emitter is configured to emit laser light energy atwavelengths of about 308 nanometers, at pulse durations between about120 nanoseconds and about 140 nanoseconds, and at frequencies betweenabout 25 pulses per second to about 80 pulses per second.

A method according to any of paragraphs [0026]-[0028], wherein theliquid medium is any one of iodine-containing contrast medium orgadolinium contrast medium.

A method according to any of paragraphs [0026]-[0029], wherein theinflation pressure obtained by delivering liquid medium into thedilation balloon catheter is between about 0.25 atmospheres and about5.0 atmospheres of pressure.

The present disclosure provides a method for treating an obstruction orrestriction within the vasculature of a subject, the method comprisingpositioning a catheter within the vasculature of a subject, the cathetercomprising a lumen, a proximal end and a distal end, one or moreemitters circumferentially arranged around or adjacent to the lumen, aballoon circumferentially arranged around a portion of the catheter,wherein at least a portion of the balloon is coated with one or moretherapeutic agents, at least one energy source coupled to the at leastone emitter, wherein said emitter is coupled to the catheter anddisposed within the balloon, wherein said emitter is disposed proximateto the distal end of the catheter, wherein one or more liquid mediumports disposed about the catheter and within the balloon, wherein saidliquid medium ports are used to fill the balloon with a liquid medium,positioning the balloon adjacent to an obstruction or restriction withinthe vasculature, inflating the balloon by delivering a liquid mediumthrough an inner lumen of the catheter and out one or more liquid mediumports into the balloon until a desired inflation pressure is obtained,and activating the at least one energy source to emit one or more pulsesof light energy from the at least one emitter within the balloon,wherein emitting the one or more pulses of light energy from the atleast one emitter reacts with the liquid medium and generates aplurality of propagating laser-induced pressure waves that delivers theone or more therapeutic agents to the vascular obstruction orrestriction or to the tissues surrounding the vascular obstruction orrestriction.

A method according to paragraph [0031], wherein the plurality ofpropagating laser-induced pressure waves enhances the penetration of theone or more therapeutic agents into the vascular obstruction orrestriction or into the tissues surrounding the vascular obstruction orrestriction.

A method according to any of paragraphs [0031]-[0032], wherein the atleast one emitter is configured to emit light energy at wavelengths ofbetween about 300 nanometers to about 350 nanometers, at pulse durationsbetween about 100 nanoseconds to about 150 nanoseconds, and atfrequencies between about 1 pulse to about 250 pulses per second.

A method according to any of paragraphs [0031]-[0033], wherein the atleast one emitter is configured to emit laser light energy atwavelengths of about 308 nanometers, at pulse durations between about120 nanoseconds and about 140 nanoseconds, and at frequencies betweenabout 25 pulses per second to about 80 pulses per second.

A method according to any of paragraphs [0031]-[0034], wherein theliquid medium is contrast medium or contrast solution, wherein theliquid medium is any one of iodine-containing contrast medium orgadolinium contrast medium, and/or wherein the liquid medium isconfigured to exhibit high absorption of light energy emitted from theat least one emitter at wavelengths of between about 1 nanometer toabout 1 millimeter, at pulse durations between about 1 nanosecond toabout 1 second, and at frequencies between about 1 pulse per second toabout 1000 pulses per second.

A method according to any of paragraphs [0031]-[0035], wherein theliquid medium is delivered into the balloon catheter to create apressure greater than 0.0 atmospheres to about 20.0 atmospheres withinthe balloon catheter.

A method according to any of paragraphs [0031]-[0036], wherein the oneor more therapeutic agents comprises one or more oxidation-insensitivedrugs in a polymer-free drug preparation.

A method according to any of paragraphs [0031]-[0037], wherein the oneor more oxidation-insensitive drugs is one or more of taxanes,thalidomide, statins, corticoids, and lipophilic derivatives ofcorticoids.

The present disclosure also provides a catheter having a guidewirelumen, an inflation lumen, a proximal end and a distal end, one or moreemitters circumferentially arranged around or adjacent to the lumen, aballoon circumferentially arranged around a portion of the catheter, atleast one energy source coupled to the at least one emitter, a means fordirecting a laser-induced pressure wave and/or cavitation event towardsthe guidewire lumen or a guidewire within the guidewire lumen, whereinsaid emitter is coupled to the catheter and disposed within the balloon,wherein said emitter is disposed proximate to the distal end of thecatheter, wherein one or more liquid medium ports disposed about thecatheter and within the balloon, wherein said liquid medium ports areused to fill the balloon with a liquid medium.

A catheter according to paragraph [0039], wherein the means fordirecting a laser-induced pressure wave and/or cavitation event towardsthe guidewire lumen or a guidewire within the guidewire lumen comprisesan outer band coupled to the distal end of the catheter, wherein theouter band comprises a distal end, and the emitter is disposed proximatethe distal end of the outer band.

A catheter according to any of paragraphs [0039]-[0040], wherein theemitter is directed at the guidewire lumen or a guidewire.

A catheter according to any of paragraphs [0039]-[0041], wherein themeans for directing a laser-induced pressure wave and/or cavitationevent towards the guidewire lumen or a guidewire comprises a cap coupledto the distal end of the catheter.

A catheter according to any of paragraphs [0039]-[0042], wherein the capis configured to direct a laser-induced pressure wave and/or cavitationevent towards the guidewire lumen or a guidewire within the guidewirelumen.

A catheter according to any of paragraphs [0039]-[0043], wherein capcomprises an interior side and an exterior side, wherein the interiorside is tapered to direct a laser-induced pressure wave and/orcavitation event towards the guidewire lumen or a guidewire within theguidewire lumen.

A catheter according to any of paragraphs [0039]-[0044], wherein emitteris disposed proximate the interior side of the cap.

A catheter according to any of paragraphs [0039]-[0045], wherein the atleast one emitter is configured to emit laser light energy atwavelengths of between about 300 nanometers to about 350 nanometers, atpulse durations between about 100 nanoseconds to about 150 nanoseconds,and at frequencies between about 1 pulse per second to about 250 pulsesper second.

A catheter according to any of paragraphs [0039]-[0046], wherein the atleast one emitter is configured to emit laser light energy atwavelengths of about 308 nanometers, at pulse durations between about120 nanoseconds and about 140 nanoseconds, and at frequencies betweenabout 25 pulses per second to about 80 pulses per second.

A catheter according to any of paragraphs [0039]-[0047], wherein totalenergy output for the at least one emitter is between about 30 to about80 millijoules per millimeter squared (mJ/mm²).

A catheter according to any of paragraphs [0039]-[0048], wherein theliquid medium is contrast medium or contrast solution.

A catheter according to any of paragraphs [0039]-[0049], wherein theliquid medium is any one of iodine-containing contrast medium orgadolinium contrast medium.

A catheter according to any of paragraphs [0039]-[0050], wherein theliquid medium is configured to exhibit high absorption of light energyemitted from the at least one emitter at wavelengths of between about 1nanometer to about 1 millimeter, at pulse durations between about 1nanosecond to about 1 second, and at frequencies between about 1 pulseper second to about 1000 pulses per second.

A catheter according to any of paragraphs [0039]-[0051], wherein themeans for directing a laser-induced pressure wave and/or cavitationevent towards the guidewire lumen or a guidewire within the guidewirelumen comprises pressure-wave reflective material in the ballooncatheter such that upon the laser-induced pressure wave and/or vaporbubble reaching the pressure-wave reflective material in the ballooncatheter, the reflective material directs the laser-induced pressurewave and/or cavitation event toward the guidewire lumen and/or guidewireto excite and/or vibrate the guidewire.

A catheter according to any of paragraphs [0039]-[0052], wherein thecavitation event occurs on a guidewire within the guidewire lumen,resulting in excitation and/or vibration of the guidewire.

The present disclosure also provides a method for treating anobstruction or restriction within vasculature of a subject, the methodcomprising positioning a catheter within vasculature of a subject, thecatheter having a guidewire lumen, an inflation lumen, a proximal endand a distal end, one or more emitters circumferentially arranged aroundor adjacent to the lumen, a balloon circumferentially arranged around aportion of the catheter, at least one energy source coupled to the atleast one emitter, a means for directing a laser-induced pressure waveand/or cavitation event towards the guidewire lumen or a guidewirewithin the guidewire lumen, wherein said emitter is coupled to thecatheter and disposed within the balloon, wherein said emitter isdisposed proximate to the distal end of the catheter, wherein one ormore liquid medium ports disposed about the catheter and within theballoon, wherein said liquid medium ports are used to fill the balloonwith a liquid medium, positioning the balloon adjacent to an obstructionor restriction within the vasculature, inflating the balloon bydelivering a liquid medium through an inner lumen of the catheter andout one or more liquid medium ports into the balloon until a desiredinflation pressure is obtained, and activating the at least one energysource to emit one or more pulses of light energy from the at least oneemitter within the balloon, wherein emitting the one or more pulses oflight energy from the at least one emitter reacts with the liquid mediumand generates a plurality of propagating laser-induced pressure wavesthat engage and disrupt at least a portion of the vascular obstructionor restriction, and wherein the means for directing laser-inducedpressure wave and/or cavitation event towards the guidewire lumen or aguidewire within the guidewire lumen induces vibrations within theguidewire.

A method according to paragraph [0054], wherein the means for directinglaser-induced pressure wave and/or cavitation event towards theguidewire lumen or a guidewire within the guidewire lumen comprises anouter band coupled to the distal end of the catheter, wherein the outerband comprises a distal end, and the emitter is disposed proximate thedistal end of the outer band.

A method according to any of paragraphs [0054]-[0055], wherein theemitter is directed at the guidewire lumen or a guidewire.

A method according to any of paragraphs [0054]-[0056], wherein the meansfor directing laser-induced pressure wave and/or cavitation eventtowards the guidewire lumen or a guidewire comprises a cap coupled tothe distal end of the catheter.

A method according to any of paragraphs [0054]-[0057], wherein the capis configured to for directing laser-induced pressure wave and/orcavitation event towards the guidewire lumen or a guidewire within theguidewire lumen.

A method according to any of paragraphs [0054]-[0058], wherein capcomprises an interior side and an exterior side, wherein the interiorside is tapered to direct the laser-induced pressure wave and/orcavitation event towards the guidewire lumen or a guidewire within theguidewire lumen.

A method according to any of paragraphs [0054]-[0059], wherein emitteris disposed proximate the interior side of the cap.

A method according to any of paragraphs [0054]-[0060], wherein theballoon is deflated and the positioning, inflating, and activating stepsare repeated.

The present disclosure also provides a catheter comprising a catheterhaving a first guidewire lumen, a lumen, a proximal end and a distalend, one or more emitters circumferentially arranged around or adjacentto the lumen, a balloon circumferentially arranged around a portion ofthe catheter, at least one energy source coupled to the at least oneemitter, wherein said emitter is coupled to the catheter and disposedwithin the balloon, wherein said emitter is disposed proximate to thedistal end of the catheter, wherein one or more liquid medium portsdisposed about the catheter and within the balloon, wherein said liquidmedium ports are used to fill the balloon with a liquid medium, asealable valve having a second guidewire lumen and a seal, a balloonhaving a proximal end and distal end, wherein the proximal end of theballoon is coupled to the distal end of the catheter, wherein the distalend of the balloon is coupled to the sealable valve, and whereuponintroducing a guidewire into the first guidewire lumen and the secondguidewire lumen and introducing liquid medium through the inflationlumen and into the balloon, the liquid medium actuates the seal withinthe valve and closes an opening between the valve and the guidewire.

The catheter according to paragraph [0062], wherein the sealable valvefurther comprises an exterior wall and a flange disposed radiallytherein, wherein a gap exists between the exterior wall and the flange.

The catheter according to any of paragraphs [0062]-[0063], wherein thesealable valve comprises a proximal portion and a distal portion, andwherein the flange is disposed toward the proximal end of the sealablevalve.

The catheter according to any of paragraphs [0062]-[0063], wherein theproximal portion of the sealable valve is tubular.

The catheter according to any of paragraphs [0062]-[0063], wherein thedistal portion of the sealable valve is tapered radially inward from theexterior wall towards the second guidewire lumen.

The catheter according to any of paragraphs [0062]-[0063], whereinsealable valve further comprises openings within the exterior walltoward the proximal portion.

The catheter according to any of paragraphs [0062]-[0063], wherein theflange is tapered radially inward towards the second guidewire lumen asthe flange progresses from the distal portion toward the proximalportion.

The present disclosure also provides a system for treating anobstruction or restriction within vasculature of a subject, the systemcomprising a catheter with a first guidewire lumen, a lumen, a proximalend and a distal end, one or more emitters circumferentially arrangedaround or adjacent to the lumen, a balloon circumferentially arrangedaround a portion of the catheter, at least one energy source coupled tothe at least one emitter, wherein said emitter is coupled to thecatheter and disposed within the balloon, wherein said emitter isdisposed proximate to the distal end of the catheter, wherein one ormore liquid medium ports disposed about the catheter and within theballoon, wherein said liquid medium ports are used to fill the balloonwith a liquid medium, a sealable valve having a second guidewire lumenand a seal, a balloon having a proximal end and distal end, wherein theproximal end of the balloon is coupled to the distal end of thecatheter, wherein the distal end of the balloon is coupled to thesealable valve, and whereupon introducing a guidewire into the firstguidewire lumen and the second guidewire lumen and introducing liquidmedium through the inflation lumen and into the balloon, the liquidmedium actuates the seal within the valve and closes an opening betweenthe valve and the guidewire, and a laser catheter comprising a proximalportion, distal portion, at least one or more emitters disposed therein,wherein the at least one or more emitters extend from the proximalportion, wherein the proximal portion is coupled to an energy source,wherein the at least one emitter is disposed within the balloon.

The system according to paragraph [0069] and the catheter according toany of paragraphs [0062]-[0063], wherein the at least one emitter isconfigured to emit laser light energy at wavelengths of between about300 nanometers to about 350 nanometers, at pulse durations between about100 nanoseconds to about 150 nanoseconds, and at frequencies betweenabout 1 pulse per second to about 250 pulses per second.

The system according to any of paragraphs [0069]-[0070] and the catheteraccording to any of paragraphs [0062]-[0063], wherein the at least oneemitter is configured to emit laser light energy at wavelengths of about308 nanometers, at pulse durations between about 120 nanoseconds andabout 140 nanoseconds, and at frequencies between about 25 pulses persecond to about 80 pulses per second.

The system according to any of paragraphs [0069]-[0070] and the catheteraccording to any of paragraphs [0062]-[0063], wherein total energyoutput for the at least one emitter is between about 30 to about 80millijoules per millimeter squared (mJ/mm2).

The present disclosure also provides a method for treating anobstruction or restriction within vasculature of a subject, the methodcomprising positioning a guidewire within vasculature of a subject,positioning a catheter within the vasculature of a subject over theguidewire, the catheter comprising a comprising a catheter with a firstguidewire lumen, a lumen, a proximal end and a distal end, one or moreemitters circumferentially arranged around or adjacent to the lumen, aballoon circumferentially arranged around a portion of the catheter, atleast one energy source coupled to the at least one emitter, whereinsaid emitter is coupled to the catheter and disposed within the balloon,wherein said emitter is disposed proximate to the distal end of thecatheter, wherein one or more liquid medium ports disposed about thecatheter and within the balloon, wherein said liquid medium ports areused to fill the balloon with a liquid medium, a sealable valve having asecond guidewire lumen and a seal, a balloon having a proximal end anddistal end, wherein the proximal end of the balloon is coupled to thedistal end of the catheter, wherein the distal end of the balloon iscoupled to the sealable valve, and whereupon introducing a guidewireinto the first guidewire lumen and the second guidewire lumen andintroducing liquid medium through the inflation lumen and into theballoon, the liquid medium actuates the seal within the valve and closesan opening between the valve and the guidewire, and introducing at leastone emitter into the balloon, activating the at least one energy sourceto emit one or more pulses of light energy from the at least one emitterwithin the balloon, wherein emitting the one or more pulses of lightenergy from the at least one emitter reacts with the liquid medium andgenerates a plurality of propagating laser-induced pressure waves thatengage and disrupt at least a portion of the vascular obstruction orrestriction.

The method according to paragraph [0073], wherein the at least oneemitter is configured to emit laser light energy at wavelengths ofbetween about 300 nanometers to about 350 nanometers, at pulse durationsbetween about 100 nanoseconds to about 150 nanoseconds, and atfrequencies between about 1 pulse per second to about 250 pulses persecond.

The method according to any of paragraphs [0073]-[0074], wherein the atleast one emitter is configured to emit laser light energy atwavelengths of about 308 nanometers, at pulse durations between about120 nanoseconds and about 140 nanoseconds, and at frequencies betweenabout 25 pulses per second to about 80 pulses per second.

The method according to any of paragraphs [0073]-[0074], wherein totalenergy output for the at least one emitter is between about 30 to about80 millijoules per millimeter squared (mJ/mm²).

The method according to any of paragraphs [0073]-[0074], wherein theliquid medium is contrast medium or contrast solution.

The method according to any of paragraphs [0073]-[0074], wherein theliquid medium is any one of iodine-containing contrast medium orgadolinium contrast medium.

The method according to any of paragraphs [0073]-[0074], wherein theliquid medium is configured to exhibit high absorption of light energyemitted from the at least one emitter at wavelengths of between about 1nanometer to about 1 millimeter, at pulse durations between about 1nanosecond to about 1 second, and at frequencies between about 1 pulseper second to about 1000 pulses per second.

According to the present disclosure, the method(s) include deliveringone or more therapeutic agents comprising one or moreoxidation-insensitive drugs in a polymer-free drug preparation,including one or more of taxanes, thalidomide, statins, corticoids, andlipophilic derivatives of corticoids. The therapeutic agents may alsoinclude one or more lipophilic antioxidants, such asnordihydroguaiaretic acid, resveratrol and propyl gallate in apolymer-free preparation. For example, U.S. application Ser. No.13/628,608, which is a continuation of International Application No.PCT/EP2010/066754, filed Nov. 3, 2010, both of which are herebyincorporated herein by reference in their entireties for all that theyteach and for all purposes, discloses a scoring or cutting ballooncatheter providing improved adherence of therapeutic agents to theballoon catheter using a combination of an oxidation-insensitive drugand a lipophilic antioxidant.

Additionally, U.S. application Ser. No. 13/707,401, filed Dec. 6, 2012,and issued on Oct. 21, 2014, which is a divisional application of U.S.application Ser. No. 11/411,635, filed Apr. 26, 2006, and which claimspriority to U.S. Provisional Application Ser. No. 60/680,450, filed May11, 2005, all of which are hereby incorporated herein by reference intheir entireties for all that they teach and for all purposes, disclosesscoring elements of a balloon catheter coated with a polymer matrix todeliver hydrophobic and lipophilic drugs to regions within a thrombus orplaque.

Additionally, U.S. application Ser. No. 13/310,320, filed Dec. 2, 2011,and issued Oct. 22, 2013, which is a divisional application of U.S.application Ser. No. 12/712,134, filed Feb. 24, 2010, and issued Mar. 6,2012, and U.S. application Ser. No. 12/726,101, filed Mar. 17, 2010, andissued Feb. 14, 2012, which is a continuation-in-part of U.S.application Ser. No. 12/712,134, filed Feb. 24, 2010, and issued Mar. 6,2012, which is a continuation-in-part of U.S. application Ser. No.12/558,420, filed Sep. 11, 2009, which is a continuation-in-part of U.S.application Ser. No. 12/210,344, filed Sep. 15, 2008, and issued Sep. 4,2012, and U.S. application Ser. No. 14/149,862, filed Jan. 8, 2014,which is a continuation of U.S. application Ser. No. 13/560,538, filedJun. 27, 2012, and issued Mar. 18, 2014, which is a divisionalapplication of U.S. application Ser. No. 12/210,344, filed Sep. 15,2008, and issued Sep. 4, 2012, all of which are hereby incorporatedherein by reference in their entireties for all that they teach and forall purposes, disclose methods and devices for local delivery ofwater-soluble and water-insoluble therapeutic agents to the surface ofnormal and diseased body lumens.

Additionally, U.S. application Ser. No. 13/926,515, filed Jun. 25, 2013,which claims priority to U.S. Provisional Application Ser. No.61/665,758, filed Jun. 28, 2012, both of which are hereby incorporatedherein by reference in their entireties for all that they teach and forall purposes, disclose methods and devices for coating a medical devicethat includes a therapeutic agent dispersed in a polymer or oligomermatrix.

The present disclosure also provides a catheter comprising a lumen, aproximal end and a distal end, one or more emitters circumferentiallyarranged around or adjacent to the lumen, a balloon circumferentiallyarranged around a portion of the catheter, at least one energy sourcecoupled to the at least one emitter, wherein said emitter is coupled tothe catheter and disposed within the balloon, wherein said emitter isdisposed proximate to the distal end of the catheter, wherein one ormore inflation ports disposed about the catheter and within the balloon,wherein said inflation ports are used to fill the balloon with ainflation medium, and a light absorbing material located within theballoon catheter such that the light absorbing material interacts withlight emitted from at least one emitter.

A catheter according to paragraph [0084], wherein the at least oneemitter is configured to emit laser light energy at wavelengths ofbetween about 300 nanometers to about 350 nanometers, at pulse durationsbetween about 100 nanoseconds to about 150 nanoseconds, and atfrequencies between about 1 pulse per second to about 250 pulses persecond.

A catheter according to paragraphs [0084] or [0085], wherein the atleast one emitter is configured to emit laser light energy atwavelengths of about 308 nanometers, at pulse durations between about120 nanoseconds and about 140 nanoseconds, and at frequencies betweenabout 25 pulses per second to about 80 pulses per second.

A catheter according to any of paragraphs [0084]-[0086], wherein totalenergy output for the at least one emitter is between about 30 to about80 millijoules per millimeter squared (mJ/mm²).

A catheter according to any of paragraphs [0084]-[0087] furthercomprising additional emitters within the catheter, the additionalemitters having a distal end corresponding to the distal end of thecatheter, the distal end of the additional emitters being disposeddistally of the balloon catheter

A catheter according to any of paragraphs [0084]-[0088], wherein theadditional emitters within the catheter are configured to emit laserlight energy at wavelengths between about 300 nanometers to about 350nanometers, at pulse durations between about 100 nanoseconds to about150 nanoseconds, and at frequencies between about 1 pulse per second toabout 250 pulses per second.

A catheter according to any of paragraphs [0084]-[0089], wherein the oneor more inflation medium ports are used to deliver an inflation mediuminto the balloon catheter to inflate the balloon catheter.

A catheter according to any of paragraphs [0084]-[0090], wherein theinflation medium is a liquid medium comprising saline, or wherein theinflation medium is a gas medium comprising an inert gas.

A catheter according to any of paragraphs [0084]-[0091], wherein thelight absorbing material is configured to exhibit high absorption oflight energy emitted from the at least one emitter at wavelengths ofbetween about 1 nanometer to about 1 millimeter, at pulse durationsbetween about 1 nanosecond to about 1 second, and at frequencies betweenabout 1 pulse per second to about 1000 pulses per second.

A catheter according to any of paragraphs [0084]-[0092], wherein thelight absorbing material is applied as a coating to a support structurelocated within the balloon catheter.

A catheter according to any of paragraphs [0084]-[0093], wherein the atleast one emitter is two or more concentric emitters.

A catheter according to any of paragraphs [0084]-[0094], wherein the atleast one emitter is two or more single-fiber emitters.

A catheter according to any of paragraphs [0084]-[0095], wherein the atleast one emitter is configured to translate within the ballooncatheter.

The present disclosure also provides a method for treating anobstruction or restriction within vasculature of a subject. The methodcomprises positioning a catheter within vasculature of a subject, acatheter comprising a lumen, a proximal end and a distal end, one ormore emitters circumferentially arranged around or adjacent to thelumen, a balloon circumferentially arranged around a portion of thecatheter, at least one energy source coupled to the at least oneemitter, wherein said emitter is coupled to the catheter and disposedwithin the balloon, wherein said emitter is disposed proximate to thedistal end of the catheter, wherein one or more inflation ports disposedabout the catheter and within the balloon, wherein said inflation portsare used to fill the balloon with a inflation medium, and a lightabsorbing material located within the balloon catheter such that thelight absorbing material interacts with light emitted from at least oneemitter. The method also provides positioning the balloon catheteradjacent an obstruction or restriction within the vasculature, inflatingthe balloon catheter by delivering inflation medium through an innerlumen of the catheter and out one or more inflation medium ports intothe balloon catheter until a desired inflation pressure is obtained, andactivating the at least one emitter within the balloon catheter totransmit a pulse of light energy such that the light energy interactswith at least a portion of the light absorbing material, wherein thelight energy reacts with the light absorbing material to generate aplurality of pressure waves which engage and disrupt at least a portionof the vascular obstruction or restriction.

The method according to paragraph [0097], wherein the at least oneemitter is configured to emit light energy at wavelengths of betweenabout 300 nanometers to about 350 nanometers, at pulse durations betweenabout 100 nanoseconds to about 150 nanoseconds, and at frequenciesbetween about 1 pulse per second to about 250 pulses per second.

The method according to paragraphs [0097]-[0098], wherein the lightabsorbing material is configured to exhibit high absorption of lightenergy emitted from the at least one emitter at wavelengths of betweenabout 1 nanometer to about 1 millimeter, at pulse durations betweenabout 1 nanosecond to about 1 second, and at frequencies between about 1pulse per second to about 1000 pulses per second.

The method according to any of paragraphs [0097]-[0099], wherein thelight absorbing material is applied as a coating to a support structurelocated within the balloon catheter.

The present disclosure also provides a method for treating anobstruction or restriction within vasculature of a subject. The methodcomprises positioning a catheter within vasculature of a subject, acatheter comprising a lumen, a proximal end and a distal end, one ormore emitters circumferentially arranged around or adjacent to thelumen, a balloon circumferentially arranged around a portion of thecatheter, at least one energy source coupled to the at least oneemitter, wherein said emitter is coupled to the catheter and disposedwithin the balloon, wherein said emitter is disposed proximate to thedistal end of the catheter, wherein one or more inflation ports disposedabout the catheter and within the balloon, wherein said inflation portsare used to fill the balloon with a inflation medium, and a lightabsorbing material located within the balloon catheter such that thelight absorbing material interacts with light emitted from at least oneemitter. The method also provides positioning the balloon catheteradjacent an obstruction or restriction within the vasculature, inflatingthe balloon catheter by delivering inflation medium through an innerlumen of the catheter and out one or more inflation medium ports intothe balloon catheter until a desired inflation pressure is obtained, andactivating the at least one emitter within the balloon catheter totransmit a pulse of light energy such that the light energy interactswith at least a portion of the light absorbing material, wherein thelight energy reacts with the light absorbing material to generate aplurality of pressure waves that deliver one or more therapeutic agentsto the vascular obstruction or restriction or to the tissues surroundingthe vascular obstruction or restriction.

The method according to paragraph [00101], wherein the plurality ofpressure waves enhances the penetration of the one or more therapeuticagents into the vascular obstruction or restriction or into the tissuessurrounding the vascular obstruction or restriction.

The method according to paragraphs [00101]-[00102], wherein the at leastone emitter is configured to emit light energy at wavelengths of betweenabout 300 nanometers to about 350 nanometers, at pulse durations betweenabout 100 nanoseconds to about 150 nanoseconds, and at frequenciesbetween about 1 pulse to about 250 pulses per second.

The method according to any of paragraphs [00101]-[00103], wherein thelight absorbing material is configured to exhibit high absorption oflight energy emitted from the at least one emitter at wavelengths ofbetween about 1 nanometer to about 1 millimeter, at pulse durationsbetween about 1 nanosecond to about 1 second, and at frequencies betweenabout 1 pulse per second to about 1000 pulses per second.

The method according to any of paragraphs [00101]-[00104], wherein thelight absorbing material is applied as a coating to a support structurelocated within the balloon catheter.

The present disclosure provides a catheter comprising of a lumen, aproximal end and a distal end, one or more emitters circumferentiallyarranged around or adjacent to the lumen, a balloon circumferentiallyarranged around a portion of the catheter, at least one energy sourcecoupled to the at least one emitter, wherein said emitter is coupled tothe catheter and disposed within the balloon, wherein said emitter isdisposed proximate to the distal end of the catheter, wherein one ormore liquid medium ports disposed about the catheter and within theballoon, wherein said liquid medium ports are used to fill the balloonwith a liquid medium, and a pressure-wave reflective element disposedadjacent to the balloon, wherein the pressure-wave reflective elementattenuates the vapor bubble generated within the balloon catheter by thereaction between laser light emitted by the emitter and a liquid mediumintroduced into the balloon via the one or more liquid medium ports.

The catheter according to paragraph [00106], wherein the pressure-wavereflective element is integrally disposed within the balloon catheter.

The catheter according to any of paragraphs [00106]-[00107], wherein theballoon catheter has an exterior, and wherein the pressure-wavereflective element is disposed on the exterior of the balloon catheter.

The catheter according to any of paragraphs [00106]-[00108], wherein theballoon catheter has an interior, and wherein the pressure-wavereflective element is disposed on the interior of the balloon catheter.

The catheter according to any of paragraphs [00106]-[00109], wherein thepressure-wave reflective element comprises a plurality of openings.

The catheter according to any of paragraphs [00106]-[00110], wherein theplurality of openings are between 10 microns and 10 millimeters.

The catheter according to any of paragraphs [00106]-[00111], wherein apercentage of the openings within an area of a portion of thepressure-wave reflective element is between 10 percent and 90 percent.

The catheter according to any of paragraphs [00106]-[00112], wherein anarea of the pressure-wave reflective element comprises the openings anda structural mass, wherein a ratio of the openings to the structuralmass within the area is between 10:1 and 1:10.

The catheter according to any of paragraphs [00106]-[00113], wherein theplurality of openings comprise at least one of the following shapes:circle; oval; triangle; square; rectangle; polygon; diamond; pentagon;hexagon; heptagon; octagon; nonagon; and decagon.

The catheter according to any of paragraphs [00106]-[00114], wherein atleast one emitter is configured to emit laser light energy atwavelengths of between about 300 nanometers to about 350 nanometers, atpulse durations between about 100 nanoseconds to about 150 nanoseconds,and at frequencies between about 1 pulse per second to about 250 pulsesper second.

The catheter according to any of paragraphs [00106]-[0015], wherein atleast one emitter is configured to emit laser light energy atwavelengths of about 308 nanometers, at pulse durations between about120 nanoseconds and about 140 nanoseconds, and at frequencies betweenabout 25 pulses per second to about 80 pulses per second.

The catheter according to any of paragraphs [00106]-[00116], whereintotal energy output for the at least one emitter is between about 30 toabout 80 millijoules per millimeter squared (mJ/mm2).

A catheter according to any of paragraphs [00106]-[00117], wherein thetotal energy output for the at least one emitter is between about 20 toabout 1000 millijoules per millimeter squared (mJ/mm²).

The catheter according to any of paragraphs [00106]-[00118], wherein theliquid medium is contrast medium or contrast solution.

The catheter according to any of paragraphs [00106]-[00119], wherein theliquid medium is any one of iodine-containing contrast medium orgadolinium contrast medium.

The catheter according to any of paragraphs [00106]-[00120], wherein theliquid medium is configured to exhibit high absorption of light energyemitted from the at least one emitter at wavelengths of between about 1nanometer to about 1 millimeter, at pulse durations between about 1nanosecond to about 1 second, and at frequencies between about 1 pulseper second to about 1000 pulses per second.

The present disclosure also provides a method for treating anobstruction or restriction within vasculature of a subject, the methodcomprising positioning a catheter within vasculature of a subject, acatheter comprising of a lumen, a proximal end and a distal end, one ormore emitters circumferentially arranged around or adjacent to thelumen, a balloon circumferentially arranged around a portion of thecatheter, at least one energy source coupled to the at least oneemitter, wherein said emitter is coupled to the catheter and disposedwithin the balloon, wherein said emitter is disposed proximate to thedistal end of the catheter, wherein one or more liquid medium portsdisposed about the catheter and within the balloon, wherein said liquidmedium ports are used to fill the balloon with a liquid medium, and apressure-wave reflective element disposed adjacent to the balloon,wherein the pressure-wave reflective element attenuates the vapor bubblegenerated within the balloon catheter by the reaction between laserlight emitted by the emitter and a liquid medium introduced into theballoon via the one or more liquid medium ports, positioning the ballooncatheter adjacent to an obstruction or restriction within thevasculature, inflating the balloon catheter by delivering a liquidmedium through the inflation lumen and out one or more liquid mediumports into the balloon catheter until a desired inflation pressure isobtained, and activating the at least one energy source to emit at leastone pulse of light energy from the emitter within the balloon, whereuponthe light energy reacts with the liquid medium and generates one or morelaser-induced pressure waves that propagate through the balloon anddisrupt at least a portion of the vascular obstruction or restriction,wherein the pressure-wave reflective element attenuates the vaporbubble.

The catheter according to paragraph [00122], wherein the pressure-wavereflective element is integrally disposed within the balloon catheter.

The catheter according to any of paragraphs [00122]-[00123], wherein theballoon catheter has an exterior, and wherein the pressure-wavereflective element is disposed on the exterior of the balloon catheter.

The catheter according to any of paragraphs [00122]-[00124], wherein theballoon catheter has an interior, and wherein the pressure-wavereflective element is disposed on the interior of the balloon catheter.

The catheter according to any of paragraphs [00122]-[00125], wherein thepressure-wave reflective element comprises a plurality of openings.

The method according to any of paragraphs [00122]-[00126], wherein theplurality of openings are between 10 microns and 10 millimeters.

The method according to any of paragraphs [00122]-[00127], wherein apercentage of the openings within an area of a portion of thepressure-wave reflective element is between 10 percent and 90 percent.

The method according to any of paragraphs [00122]-[00128], wherein anarea of the pressure-wave reflective element comprises the openings anda structural mass, wherein a ratio of the openings to the structuralmass within the area is between 10:1 and 1:10.

The method according to any of paragraphs [00122]-[00129], wherein theplurality of openings comprise at least one of the following shapes:circle; oval; triangle; square; rectangle; polygon; diamond; pentagon;hexagon; heptagon; octagon; nonagon; and decagon.

The method according to any of paragraphs [00122]-[00130] furthercomprising the step of re-positioning the balloon catheter such that theballoon is adjacent another portion of the obstruction or restriction.

The method according to any of paragraphs [00122]-[00131] furthercomprising the step of moving the at least one emitter within theballoon catheter.

The method according to any of paragraphs [00122]-[00132], wherein theat least one emitter is moving within the pressure-wave reflectiveelement.

The method according to any of paragraphs [00122]-[00133] furthercomprising the step of re-positioning the at least one emitter withinthe balloon catheter.

The method according to any of paragraphs [00122]-[00134] furthercomprising the step of re-positioning the at least one emitter withinthe pressure-wave reflective element.

The method according to any of paragraphs [00122]-[00135] furthercomprising the steps of removing the catheter from the vasculature.

The method according to any of paragraphs [00122]-[00136] furthercomprising the step of inserting a drug-coated balloon into thevasculature such that the drug-coated balloon is disposed adjacent aremaining portion of the occlusion.

The method according to any of paragraphs [00122]-[00137] furthercomprising the step of inflating the drug-coated balloon and applying adrug disposed on the drug-coated balloon to the remaining portion of theocclusion.

The present disclosure also provides a catheter system comprising aballoon catheter, comprising a catheter having a proximal end and adistal end and a lumen therein, and a balloon coupled to the catheter,wherein one or more liquid medium ports disposed about the catheter andwithin the balloon, wherein said liquid medium ports are used to fillthe balloon with a liquid medium, a laser catheter comprising a proximalportion, distal portion, at least one or more emitters disposed therein,wherein the at least one or more emitters extend from the proximalportion, wherein the proximal portion is coupled to an energy source,wherein the at least one emitter is disposed within the balloon, a meansfor introducing a liquid medium into the balloon, a handle comprising abase coupled to the proximal end of the catheter, and a drive mechanismtranslatably coupled to the base, the drive mechanism coupled to thelaser catheter such that translation of the drive mechanism relative tothe base causes translation of the laser catheter within the lumen ofthe catheter and within the balloon.

The catheter system according to paragraph [00139], wherein the drivemechanism comprises a control element movably coupled to the base; and acoupling translatably coupled to the base and driven by the controlelement, the coupling coupled to the laser catheter such that movementof the control element relative to the base causes translation of thelaser catheter within the lumen of the catheter and within the balloon.

The catheter system according to paragraph [00139]-[00140], wherein thecontrol element is rotatably coupled to the base, and rotation of thecontrol element relative to the base causes translation of the lasercatheter within the lumen of the catheter and within the balloon.

The catheter system according to paragraph [00139]-[00141], wherein thecontrol element includes a first threaded surface, and the drivemechanism further includes a shaft that is translatable within the baseand coupled to the coupling, the shaft including a second threadedsurface, and the second threaded surface coupling to the first threadedsurface such that rotation of the control element relative to the basecauses translation of the shaft within the base and translation of thelaser catheter within the lumen of the catheter and within the balloon.

The catheter system according to paragraph [00139]-[00142], wherein thehandle further comprises a tube coupled to the base, the tube receivingthe laser catheter, and wherein the shaft includes an inner lumen thattranslatably receives the tube as the shaft translates within the base.

The catheter system according to paragraph [00139]-[00143], wherein thedrive mechanism further comprises a seal coupled to the shaft, the sealtranslatably engaging the tube.

The catheter system according to paragraph [00139]-[00144], wherein thetube is a hypotube.

The catheter system according to paragraph [00139]-[00145], wherein thebase includes a first key feature, the shaft includes a second keyfeature that couples to the first key feature to inhibit rotation of theshaft relative to the base.

The catheter system according to paragraph [00139]-[00146], wherein thebase includes an opening disposed within the control element, the secondthreaded surface extending through the opening to couple to the firstthreaded surface.

The present disclosure also provides for a handle for coupling to acatheter and a laser catheter, the handle comprising a base configuredto couple to a proximal end of the catheter, and a drive mechanismtranslatably coupled to the base, the drive mechanism configured tocouple to the laser catheter such that translation of the drivemechanism relative to the base causes translation of the laser catheterwithin a lumen of the catheter and within a balloon coupled to thecatheter.

The handle according to paragraph [00148], wherein the drive mechanismcomprises a control element movably coupled to the base, and a couplingtranslatably coupled to the base and driven by the control element, thecoupling being configured to couple to the laser catheter such thatmovement of the control element relative to the base causes translationof the laser catheter within the lumen of the catheter and within theballoon.

The handle according to any of paragraphs [00148]-[00149], wherein thecontrol element is rotatably coupled to the base, and rotation of thecontrol element relative to the base causes translation of the lasercatheter within the lumen of the catheter and within the balloon.

The handle according to any of paragraphs [00148]-[00150], wherein thecontrol element includes a first threaded surface, and the drivemechanism further includes a shaft that is translatable within the baseand coupled to the coupling, the shaft including a second threadedsurface, and the second threaded surface coupling to the first threadedsurface such that rotation of the control element relative to the basecauses translation of the shaft within the base and translation of thelaser catheter within the lumen of the catheter and within the balloon.

The handle according to any of paragraphs [00148]-[00151], wherein thehandle further comprises a tube coupled to the base, the tube receivingthe laser catheter, and wherein the shaft includes an passageway thattranslatably receives the tube as the shaft translates within the baseand within the balloon.

The handle according to any of paragraphs [00148]-[00152], wherein thedrive mechanism further comprises a seal coupled to the shaft, the sealtranslatably engaging the tube.

The handle according to any of paragraphs [00148]-[00153], wherein thetube is a hypotube.

The handle according to any of paragraphs [00148]-[00154], wherein thebase includes a first key feature, the shaft includes a second keyfeature that couples to the first key feature to inhibit rotation of theshaft relative to the base.

The handle according to any of paragraphs [00148]-[00155], wherein thebase includes an opening disposed within the control element, the secondthreaded surface extending through the opening to couple to the firstthreaded surface.

The present disclosure also provides a catheter system comprising aballoon catheter having a proximal end and a distal end and a lumentherein, and a balloon coupled to the catheter, wherein one or moreliquid medium ports disposed about the catheter and within the balloon,wherein said liquid medium ports are used to fill the balloon with aliquid medium, a laser catheter comprising a proximal portion, distalportion, at least one or more emitters disposed therein, wherein the atleast one or more emitters extend from the proximal portion, wherein theproximal portion is coupled to an energy source, wherein the at leastone emitter is disposed within the balloon, a means for introducing aliquid medium into the balloon, a handle comprising a base coupled tothe proximal end of the catheter, and a drive mechanism translatablycoupled to the base, the drive mechanism coupled to the laser cathetersuch that translation of the drive mechanism relative to the base causestranslation of the laser catheter within the lumen of the catheter andwithin the balloon, positioning the balloon adjacent to an obstructionor restriction within the vasculature, inflating the balloon bydelivering a liquid medium through an inner lumen of the catheter andout one or more liquid medium ports into the balloon until a desiredinflation pressure is obtained, and activating the at least one energysource to emit one or more pulses of light energy from the at least oneemitter within the balloon, wherein emitting the one or more pulses oflight energy from the at least one emitter reacts with the liquid mediumand generates a plurality of propagating laser-induced pressure wavesthat engage and disrupt at least a portion of the vascular obstructionor restriction, and actuating the handle and sliding the at least oneemitter within the balloon.

The method according to paragraph [00157] further incorporating thestructure or steps of any of paragraphs [0011]-[00158].

The present disclosure provides a method for treating an obstruction orrestriction within the vasculature of a subject, the method comprisingpositioning a catheter within the vasculature of a subject, the cathetercomprising a lumen, a proximal end and a distal end, one or moreemitters circumferentially arranged around or adjacent to the lumen, aballoon circumferentially arranged around a portion of the catheter, atleast one energy source coupled to the at least one emitter, whereinsaid emitter is coupled to the catheter and disposed within the balloon,wherein said emitter is disposed proximate to the distal end of thecatheter, wherein one or more liquid medium ports disposed about thecatheter and within the balloon, wherein said liquid medium ports areused to fill the balloon with a gas-saturated liquid medium positioningthe balloon adjacent to an obstruction or restriction within thevasculature, inflating the balloon by delivering a gas-saturated liquidmedium through an inner lumen of the catheter and out one or more liquidmedium ports into the balloon until a desired inflation pressure isobtained, and activating the at least one energy source to emit one ormore pulses of light energy from the at least one emitter within theballoon, wherein emitting the one or more pulses of light energy fromthe at least one emitter reacts with the gas-saturated liquid medium andgenerates a plurality of propagating laser-induced pressure waves thatengage and disrupt at least a portion of the vascular obstruction orrestriction.

The method according to paragraph [00159] wherein the at least oneemitter is configured to emit light energy at wavelengths of betweenabout 300 nanometers to about 350 nanometers, at pulse durations betweenabout 100 nanoseconds to about 150 nanoseconds, and at frequenciesbetween about 1 pulse per second to about 250 pulses per second.

The method according to any of paragraphs [00159]-[00160], wherein thegas-saturated liquid medium is any one of iodine-containing contrastmedium or gadolinium contrast medium.

The method according to any of paragraphs [00159]-[00161], wherein thegas-saturated liquid medium comprises a super saturated liquid medium.

The method according to any of paragraphs [00159]-[00162], wherein theinflation pressure obtained by delivering liquid medium into thedilation balloon catheter is greater than 0.0 atmospheres and up toabout 20.0 atmospheres of pressure.

The present disclosure provides a method for improving the compliance ofa blood vessel within a subject, the method comprising locating acalcified portion in the media and/or the intima of the blood vessel ofthe subject, positioning a catheter within the blood vessel, thecatheter comprising a tube having a lumen, a proximal end and a distalend, one or more emitters arranged around or adjacent to the lumen,wherein the emitters have respective distal ends disposed adjacent thedistal end of the tube, a balloon circumferentially arranged around aportion of the distal end of the tube, and one or more liquid mediumports disposed about the catheter and within the balloon, positioningthe balloon adjacent the calcified portion in the media and/or theintima, inflating the balloon by delivering a liquid medium through aninner lumen of the tube and out one or more liquid medium ports into theballoon until a desired inflation pressure is obtained, and emitting oneor more pulses of light energy from the distal end of the emitters,wherein the one or more pulses of light energy reacts with the liquidmedium and generates a plurality of propagating laser-induced pressurewaves that disrupt the calcified portion of media and/or intima, therebyimproving the compliance of the blood vessel.

The method according to paragraph [00164], wherein the at one or morepulses of light energy comprises a wavelength of between about 300nanometers to about 350 nanometers, at pulse durations between about 100nanoseconds to about 150 nanoseconds, and at frequencies between about 1pulse per second to about 250 pulses per second.

The method according to any of paragraphs [00164]-[00165], wherein theliquid medium is any one of iodine-containing contrast medium orgadolinium contrast medium.

The method according to any of paragraphs [00164]-[00166], wherein theinflation pressure obtained by delivering liquid medium into thedilation balloon is between about 0.25 atmospheres and about 5.0atmospheres of pressure.

The method according to any of paragraphs [00164]-[00167], wherein theplurality of propagating laser-induced pressure waves enhancespenetration of one or more therapeutic agents into the media and/or theintima.

The method according to any of paragraphs [00164]-[00168], wherein theone or more therapeutic agents comprises one or moreoxidation-insensitive drugs in a polymer-free drug preparation.

The method according to any of paragraphs [00164]-[00169], wherein theone or more oxidation-insensitive drugs is one or more of taxanes,thalidomide, statins, corticoids, and lipophilic derivatives ofcorticoids.

The method according to any of paragraphs [00164]-[00170], wherein theone or more pulses of light energy comprises a wavelength a of about 308nanometers, at pulse durations between about 120 nanoseconds and about140 nanoseconds, and at frequencies between about 25 pulses per secondto about 80 pulses per second.

The method according to any of paragraphs [00164]-[00171], wherein totalenergy output for the one or more pulses of light energy comprisesenergy between about 30 to about 80 millijoules per millimeter squared(mJ/mm2).

The present disclosure provides a method for disrupting a calcifiedportion contained within the media and/or the intima of a blood vesselwall of a subject, the method comprising positioning a catheter withinthe blood vessel of the subject, the catheter comprising a tube having aguidewire lumen, an inflation lumen, a proximal end and a distal end, aplurality of emitters circumferentially arranged around or adjacent tothe guidewire lumen, wherein at least a portion of the plurality ofemitters comprises a distal end, a balloon circumferentially arrangedaround a portion of the tube and around at least a portion of the distalend of the emitters, one or more liquid medium ports disposed within thetube and within the balloon; and a pressure-wave reflective elementdisposed adjacent the balloon, positioning the balloon adjacent thecalcified portion in the media and/or the intima of the blood vessel,inflating the balloon by delivering a liquid medium through theinflation lumen and out one or more liquid medium ports into the balloonuntil a desired inflation pressure is obtained, and emitting at leastone pulse of light energy from the distal end of the emitters, whereuponthe light energy reacts with the liquid medium and generates one or morelaser-induced pressure waves that propagate through the balloon anddisrupt the calcified portion in the media and/or the intima, whereinthe pressure-wave reflective element reduces formation of vapor bubblesarising from the laser-induced pressure wave.

The method according to paragraphs [00173], wherein the pressure-wavereflective element comprises a plurality of openings.

The method according to any of paragraphs [00173]-[0174], wherein theplurality of openings are between 10 microns and 10 millimeters.

The method according to any of paragraphs [00173]-[0175], wherein apercentage of the openings within an area of a portion of thepressure-wave reflective element is between 10 percent and 90 percent.

The method according to any of paragraphs [00173]-[0176], wherein anarea of the pressure-wave reflective element comprises the openings anda structural mass, wherein a ratio of the openings to the structuralmass within the area is between 10:1 and 1:10.

The method according to any of paragraphs [00173]-[0177], wherein theplurality of openings comprise at least one of the following shapes:circle; oval; triangle; square; rectangle; polygon; diamond; pentagon;hexagon; heptagon; octagon; nonagon; and decagon.

The method according to any of paragraphs [00173]-[0178] furthercomprising the step of re-positioning the balloon such that the balloonis adjacent another portion of the obstruction or restriction.

The method according to any of paragraphs [00173]-[0179], furthercomprising the step of moving the plurality of emitters within theballoon.

The method according to any of paragraphs [00173]-[0180], wherein thewithin the plurality of emitters is re-positioned within thepressure-wave reflective element.

The method according to any of paragraphs [00173]-[0181], furthercomprising the step of re-positioning the plurality of emitters withinthe balloon.

The method according to any of paragraphs [00173]-[0182], wherein thewithin the plurality of emitters is re-positioned within thepressure-wave reflective element.

As used herein, “at least one,” “one or more,” and “and/or” areopen-ended expressions that are both conjunctive and disjunctive inoperation. For example, each of the expressions “at least one of A, Band C,” “at least one of A, B, or C,” “one or more of A, B, and C,” “oneor more of A, B, or C,” and “A, B, and/or C” means A alone, B alone, Calone, A and B together, A and C together, B and C together, or A, B andC together. When each one of A, B, and C in the above expressions refersto an element, such as X, Y, and Z, or class of elements, such asX₁-X_(n), Y₁-Y_(m), and Z₁-Z_(o), the phrase is intended to refer to asingle element selected from X, Y, and Z, a combination of elementsselected from the same class (for example, X₁ and X₂) as well as acombination of elements selected from two or more classes (for example,Y₁ and Z_(o)).

It is to be noted that the term “a” or “an” entity refers to one or moreof that entity. As such, the terms “a” (or “an”), “one or more” and “atleast one” can be used interchangeably herein. It is also to be notedthat the terms “comprising,” “including,” and “having” can be usedinterchangeably.

The term “catheter” as used herein generally refers to a tube that canbe inserted into a body cavity, duct, lumen, or vessel, such as thevasculature system. In most uses, a catheter is a relatively thin,flexible tube (“soft” catheter), though in some uses, it may be alarger, solid-less flexible—but possibly still flexible—catheter (“hard”catheter).

The term “balloon catheter” as used herein generally refers to thevarious types of catheters which carry a balloon for containing fluids.Balloon catheters may also be of a wide variety of inner structure, suchas different lumen design, of which there are at least three basictypes: triple lumen, dual lumen and co-axial lumen. All varieties ofinternal structure and design variation are meant to be included by useof the term “balloon catheter” herein.

The terms “emitter” as used herein refers to a fiber or an opticalcomponent (including any portion thereof, such as the end of a fiber)that emits light from a distal end of device, such as a catheter,towards a desired target. An emitter can be the output end of any devicethat transports light from an optical energy source to a target ortreatment area. These optical energy transport devices can include glassor fused silica fiber optics, plastic fiber optics, air or gas lightguides, and liquid light guides. As described herein, an emitter oremitters can be used to emit light of any wavelength. An emitter oremitters can emit light, including but not limited to, laser light,white light, visible light, infrared light, and ultraviolet light

According to the present disclosure, the catheter contains at least oneemitter, which may comprise glass or fused silica fiber optics, plasticfiber optics, air or gas light guides, and liquid light guides. Examplesof a liquid light guide, or a catheter that contain a liquid light guidecan be seen in U.S. application Ser. No. 11/923,488, filed Oct. 24, 2007and U.S. application Ser. No. 12/254,254, filed Oct. 20, 2008, both ofwhich are hereby incorporated herein by reference in their entiretiesfor all that they teach and for all purposes.

The term “laser-induced pressure wave” as used herein is a pressure wavecaused by a reaction between laser light and an absorptive material. Thelaser-induced pressure wave may be generated in a gas, liquid, or solid.

The term “pressure-wave reflective element” as used herein is anycomponent which redirects a laser-induced pressure wave.

The term “vapor bubble” as used herein is a gaseous cavity createdwithin a liquid.

The term “cavitation event” as used herein describes the rapid fluidmovement that leads to collapse of a vapor bubble to its smallestradius.

The term “means” as used herein shall be given its broadest possibleinterpretation in accordance with 35 U.S.C. §112(f). Accordingly, aclaim incorporating the term “means” shall cover all structures,materials, or acts set forth herein, and all of the equivalents thereof.Further, the structures, materials or acts and the equivalents thereofshall include all those described in the summary, brief description ofthe drawings, detailed description, abstract, and claims themselves.

The term “therapeutic agent” as used herein generally refers to anyknown or hereafter discovered pharmacologically active agent thatprovides therapy to a subject through the alleviation of one or more ofthe subject's physiological symptoms. A therapeutic agent may be acompound that occurs in nature, a chemically modified naturallyoccurring compound, or a compound that is chemically synthesized. Theagent will typically be chosen from the generally recognized classes ofpharmacologically active agents, including, but not necessarily limitedto, the following: analgesic agents; anesthetic agents; antiarthriticagents; respiratory drugs, including antiasthmatic agents; anticanceragents, including antineoplastic drugs; anticholinergics;anticonvulsants; antidepressants; antidiabetic agents; antidiarrheals;antihelminthics; antihistamines; antihyperlipidemic agents;antihypertensive agents; anti-infective agents such as antibiotics andantiviral agents; antiinflammatory agents; antimigraine preparations;antinauseants; antiparkinsonism drugs; antipruritics; antipsychotics;antipyretics; antispasmodics; antitubercular agents; antiulcer agents;antiviral agents; anxiolytics; appetite suppressants; attention deficitdisorder (ADD) and attention deficit hyperactivity disorder (ADHD)drugs; cardiovascular preparations including calcium channel blockers,CNS agents; beta-blockers and antiarrhythmic agents; central nervoussystem stimulants; cough and cold preparations, including decongestants;diuretics; genetic materials; herbal remedies; hormonolytics; hypnotics;hypoglycemic agents; immunosuppressive agents; leukotriene inhibitors;mitotic inhibitors; restenosis inhibitors; muscle relaxants; narcoticantagonists; nicotine; nutritional agents, such as vitamins, essentialamino acids and fatty acids; ophthalmic drugs such as antiglaucomaagents; parasympatholytics; psychostimulants; sedatives; steroids;sympathomimetics; tranquilizers; and vasodilators including generalcoronary, peripheral and cerebral.

The terms “vasculature” and “vascular” as used herein refer to any partof the circulatory system of a subject, including peripheral andnon-peripheral arteries and veins. Vasculature can be comprised ofmaterials such as nucleic acids, amino acids, carbohydrates,polysaccharides, lipids fibrous tissue, calcium deposits, remnants ofdead cells, cellular debris and the like.

The term “vascular occlusion” refers to buildup of fats, lipids, fibrin,fibro-calcific plaque, thrombus and other atherosclerotic tissue withinthe lumen or within the intima of an artery that either narrows orcompletely obstructs the inner lumen the artery thereby restricting orblocking normal blood flow through the artery segment.

It should be understood that every maximum numerical limitation giventhroughout this disclosure is deemed to include each and every lowernumerical limitation as an alternative, as if such lower numericallimitations were expressly written herein. Every minimum numericallimitation given throughout this disclosure is deemed to include eachand every higher numerical limitation as an alternative, as if suchhigher numerical limitations were expressly written herein. Everynumerical range given throughout this disclosure is deemed to includeeach and every narrower numerical range that falls within such broadernumerical range, as if such narrower numerical ranges were all expresslywritten herein.

The preceding is a simplified summary of the disclosure to provide anunderstanding of some aspects of the disclosure. This summary is neitheran extensive nor exhaustive overview of the disclosure and its variousaspects, embodiments, and configurations. It is intended neither toidentify key or critical elements of the disclosure nor to delineate thescope of the disclosure but to present selected concepts of thedisclosure in a simplified form as an introduction to the more detaileddescription presented below. As will be appreciated, other aspects,embodiments, and configurations of the disclosure are possibleutilizing, alone or in combination, one or more of the features setforth above or described in detail below.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings are incorporated into and form a part of thespecification to illustrate several examples of the present disclosure.These drawings, together with the description, explain the principles ofthe disclosure. The drawings simply illustrate preferred and alternativeexamples of how the disclosure can be made and used and are not to beconstrued as limiting the disclosure to only the illustrated anddescribed examples. Further features and advantages will become apparentfrom the following, more detailed, description of the various aspects,embodiments, and configurations of the disclosure, as illustrated by thedrawings referenced below.

FIG. 1 is a representative longitudinal view of the distal end of acatheter with the balloon catheter partially inflated, according to oneembodiment of the present disclosure.

FIG. 1A is a representative cross-sectional view (through plane A inFIG. 1) of the distal end of a catheter with the balloon catheter in apartially inflated configuration, according to one embodiment of thepresent disclosure.

FIG. 1B is a representative cross-sectional view (through plane B inFIG. 1) of the distal end of a catheter with the balloon catheter in apartially inflated configuration, according to one embodiment of thepresent disclosure.

FIG. 1C is a representative cross-sectional view (through plane C inFIG. 1) of the distal tip of the catheter, according to one embodimentof the present disclosure.

FIG. 2 is a representative longitudinal view of the distal end of acatheter adjacent to a vascular obstruction or restriction within avessel of a subject, according to one embodiment of the presentdisclosure.

FIG. 3A is a representative perspective view of the distal end of acatheter with multiple concentric proximal emitters, according to oneembodiment of the present disclosure.

FIG. 3B is a representative perspective view of the distal end of acatheter with multiple single-fiber proximal emitters, according to oneembodiment of the present disclosure.

FIG. 3C is a representative cross-sectional view (through plane C inFIG. 3A) of the distal end of a catheter, according to one embodiment ofthe present disclosure.

FIG. 4A is a representative perspective view of the distal end of acatheter with a translational proximal emitter in a first positionwithin a balloon catheter, according to one embodiment of the presentdisclosure.

FIG. 4B is a representative perspective view of the distal end of acatheter with a translational proximal emitter in a second positionwithin a balloon catheter, according to one embodiment of the presentdisclosure.

FIG. 4C is a representative perspective view of the distal end of acatheter with a translational proximal emitter in a third positionwithin a balloon catheter, according to one embodiment of the presentdisclosure.

FIG. 5 is a representative flow diagram of methods of treating a subjectusing a catheter, according to one embodiment of the present disclosure.

FIG. 6 is a representative end view of the distal end of a catheter withthe balloon catheter in a partially inflated configuration, according toone embodiment of the present disclosure.

FIG. 6A is a representative cross-sectional view of the distal end ofthe catheter illustrated in FIG. 6 through plan A-A, according to oneembodiment of the present disclosure.

FIG. 6A′ is a representative cross-sectional view of the distal end ofthe catheter illustrated in FIG. 6 through plan A-A, according to analternate embodiment of the present disclosure.

FIG. 7 is a representative cross-sectional view of a catheter, accordingto an alternate embodiment of the present disclosure, wherein a ballooncomprises a pressure-wave reflective material.

FIG. 8 is a representative cross-sectional view of a catheter, accordingto an alternate embodiment of the present disclosure, wherein a ballooncomprises an alternative pressure-wave reflective material.

FIG. 9 illustrates an exemplary ablation system, including a lasergenerator and a laser-induced pressure wave emitting balloon catheter.

FIG. 10 is a representative perspective view of the distal end of aballoon catheter with a laser ablation catheter slidable within theballoon and balloon catheter, according to one embodiment of the presentdisclosure.

FIG. 10A is a representative cross-sectional side view of the distal endof the balloon catheter and laser ablation catheter illustrated in FIG.10.

FIG. 10B is an enlarged representative perspective view of the distalend of the balloon catheter and laser ablation catheter illustrated inFIG. 10, wherein a sealable valve is illustrated at the distal end ofthe balloon.

FIG. 11 is an enlarged representative perspective view of the sealablevalve depicted in FIGS. 10, 10A and 10B.

FIG. 11A is an enlarged representative cross-sectional side view of thesealable valve in an unsealed configuration with respect to a guidewire.

FIG. 11B is an enlarged representative cross-sectional side view of thesealable valve in a sealed configuration with respect to a guidewire.

FIG. 12 is a representative longitudinal view of the distal end of thecatheter including a balloon catheter, according to one embodiment ofthe present disclosure.

FIG. 12A is a representative cross-sectional view (through plane A inFIG. 12) of the distal end of a catheter with the balloon in a partiallyinflated configuration, according to one embodiment of the presentdisclosure.

FIG. 13 is a representative cross-sectional side view of the distal endof the balloon catheter, including an energy absorbing material, andlaser ablation catheter.

FIG. 14 is a representative flow diagram of methods of treating asubject using a catheter having energy absorbing material, according toone embodiment of the present disclosure.

FIG. 15A is a side elevation view of a pressure-wave reflective elementcomprising a plurality of square-shaped openings, according to oneembodiment of the present disclosure.

FIG. 15B is a side elevation view of a pressure-wave reflective elementcomprising a plurality of diamond-shaped openings, according to oneembodiment of the present disclosure.

FIG. 15C is a side elevation view of a pressure-wave reflective elementcomprising a plurality of openings formed by a helical structure woundin a particular direction, according to one embodiment of the presentdisclosure.

FIG. 15D is a side elevation view of a pressure-wave reflective elementcomprising a plurality of openings formed by a helical structure woundin a particular direction, according to one embodiment of the presentdisclosure.

FIG. 15E is a side elevation view of a pressure-wave reflective elementcomprising a plurality of openings formed by a helical wound ribbons,according to one embodiment of the present disclosure.

FIG. 15F is a side elevation view of a pressure-wave reflective elementcomprising a plurality of hexagon-shaped openings, according to oneembodiment of the present disclosure.

FIG. 16A is an elevation view of a kit that includes a laser catheterradially disposed within a handle and a catheter and over a guidewire,according to one embodiment of the present disclosure.

FIG. 16B is a detail elevation view of the laser catheter and the handleof FIG. 16A at a proximal end of the handle.

FIG. 17A is a perspective view of the handle of FIG. 16A, whereinseveral external components are partially transparent to illustrateinternal components, and a shaft of the handle is shown in a proximalposition.

FIG. 17B is another perspective view of the handle of FIG. 16A, whereinseveral external components are partially transparent to illustrateinternal components, and the shaft is shown in the proximal position.

FIG. 17C is an elevation view of the handle of FIG. 16A, wherein severalexternal components are partially transparent to illustrate internalcomponents, and the shaft is shown in the proximal position.

FIG. 17D is an elevation view of the handle of FIG. 16A, wherein severalexternal components are partially transparent to illustrate internalcomponents, and the shaft is shown in an intermediate position.

FIG. 17E is an elevation view of the handle of FIG. 16A, wherein severalexternal components are partially transparent to illustrate internalcomponents, and the shaft is shown in a distal position.

FIG. 17F is a cross-sectional view of the handle of FIG. 16A, whereinthe shaft is shown in the proximal position.

FIG. 17G is a cross-sectional view of the handle of FIG. 16A, whereinthe shaft is shown in an intermediate position.

FIG. 17H is an exploded view of the handle of FIG. 16A.

FIG. 17I is a detail exploded view of the handle of FIG. 16A.

FIG. 17J is another detail exploded view of the handle of FIG. 16A.

FIG. 18A is a perspective view of a frame of the handle of FIG. 16A.

FIG. 18B is an elevation cross-sectional view of the frame along line18B-18B of FIG. 18A.

FIG. 18C is a perspective cross-sectional view of the frame along line18B-18B of FIG. 18A.

FIG. 18D is an elevation cross-sectional view of the frame along line18D-18D of FIG. 18A.

FIG. 18E is a perspective cross-sectional view of the frame along line18D-18D of FIG. 18A.

FIG. 18F is an elevation cross-sectional view of the frame along line18F-18F of FIG. 18A.

FIG. 18G is a perspective cross-sectional view of the frame along line18F-18F of FIG. 18A.

FIG. 19 is an elevation cross-sectional view of the shaft of the handleof FIG. 16A.

FIG. 20 is a cross-sectional view of an arterial wall taken along adirection perpendicular to the longitudinal axis of the arterial wall.

FIG. 20A is reduced version of the cross-sectional view of the arterialwall in FIG. 20.

FIG. 21A is a longitudinal-sectional view of a healthy arterial walltaken along a direction parallel to the longitudinal axis of thearterial wall.

FIG. 21B is a longitudinal-sectional view of an arterial wall takenalong a direction parallel to the longitudinal axis of the arterialwall, wherein the arterial wall includes fat and/or lipids.

FIG. 21C is a longitudinal-sectional view of an arterial wall takenalong a direction parallel to the longitudinal axis of the arterialwall, wherein the arterial wall includes plaque and calcium in theintima.

FIG. 21D is a longitudinal-sectional view of an arterial wall takenalong a direction parallel to the longitudinal axis of the arterialwall, wherein the arterial wall includes calcified plaque and lipids inthe intima

FIG. 21E is a longitudinal-sectional view of an arterial wall takenalong a direction parallel to the longitudinal axis of the arterialwall, wherein the arterial wall has ruptured.

FIG. 21F is a longitudinal-sectional view of an arterial wall takenalong a direction parallel to the longitudinal axis of the arterialwall, wherein the artery includes an obstruction or restriction.

FIG. 21G is a longitudinal-sectional view of an arterial wall takenalong a direction parallel to the longitudinal axis of the arterial wallwith a laser catheter removing the obstruction or restriction depictedin FIG. 21F.

FIG. 21H is a longitudinal-sectional view of an arterial wall takenalong a direction parallel to the longitudinal axis of the arterial wallwith a laser-induced balloon catheter located adjacent the remainingportion of the obstruction or restriction depicted in FIG. 21G.

FIG. 21I is a longitudinal-sectional view of an arterial wall takenalong a direction parallel to the longitudinal axis of the arterial wallafter utilizing the laser-induced balloon catheter illustrated in FIG.21H.

FIG. 22 is a method of removing an obstruction or restriction andtreating the remainder of the obstruction or restriction within theintima with a laser-induced balloon catheter.

FIG. 23A is a longitudinal-sectional view of a healthy arterial walltaken along a direction parallel to the longitudinal axis of thearterial wall similar to the arterial wall depicted in FIG. 21A.

FIG. 23B is a longitudinal-sectional view of an arterial wall takenalong a direction parallel to the longitudinal axis of the arterial wallwith calcification of the media.

FIG. 23C is a longitudinal-sectional view of an arterial wall takenalong a direction parallel to the longitudinal axis of the arterial wallwith a laser-induced balloon catheter located adjacent the portion ofthe arterial wall that includes the calcified media.

FIG. 23D is another longitudinal-sectional view of an arterial walltaken along a direction parallel to the longitudinal axis of thearterial wall.

FIG. 24 is a method of using a laser-induced balloon catheter to treatthe calcified media.

DETAILED DESCRIPTION

The present disclosure relates generally to the use of medical devicesfor the treatment of vascular conditions. In particular, the presentdisclosure provides materials and methods for using laser-inducedpressure waves to disrupt vascular blockages and to deliver therapeuticagents to the blockage area.

Referring to FIG. 1, the distal end of catheter 100 of the presentdisclosure includes one or more layers of optical fibers arrangedcircumferentially around or adjacent to an inner lumen 110. The proximalend of the catheter 100 is coupled to a laser generator, which is notshown. The one or more layers of optical fibers are housed in a flexibletubular catheter and terminate at different points of emission (such as,emitters), where the laser light energy is released and directed towardsa desired target. The inner layer of optical fibers 115 terminates atthe distal emitter 120 at the distal tip 130 of the catheter, while theouter layer of optical fibers 135 terminates at the proximal emitter 140of the catheter. The proximal laser emitter 140 is disposed proximate ofthe distal tip and contained within the balloon 150, which iscircumferentially arranged around a portion of the distal end of thecatheter excluding the distal tip 130 of the catheter and the distalemitter 140. Although the proximal laser emitter 140 is at the distalend of the catheter 100, it may be located at the central portion of thecatheter. The inner lumen 110 provides a conduit for the delivery of aliquid medium 160 that is used to inflate the balloon to a desiredpressure. The liquid medium 160 travels through the inner lumen 110until being released from one or more liquid medium ports 170 enclosedwithin the balloon 150. In the inflated or partially inflatedconfiguration, as shown in FIG. 1, the proximal laser emitter 140 is indirect contact with the liquid medium 160 such that when laser lightenergy is emitted from the proximal emitter 140, the liquid medium 160absorbs the emitted light.

Upon emitting the light into the liquid medium and the liquid mediumabsorbing the light, a laser-induced pressure wave is created in theliquid medium. The pressure wave compresses the fluid surrounding itsorigin, thereby generating a vapor bubble. As the pressure wavepropagates away from its origin, the fluid surrounding the vapor bubbledisplaces inward, collapsing the vapor bubble and creating a cavitationevent. The vapor bubble and subsequent cavitation event are byproductsof the laser-induced pressure wave. The laser-induced pressure wavepenetrates and/or passes through the balloon catheter 140, and the fluidmovement associated with the formation and collapse of the vapor bubbleexpands and then reduces the diameter of the balloon of the ballooncatheter.

FIG. 1A is a representative cross-sectional view of the distal end ofthe catheter 100 of the present disclosure taken along the planedemarcated by line A-A in FIG. 1. As shown, the distal end of thecatheter 100 includes one or more layers of optical fibers 115 arrangedcircumferentially around an inner lumen 110. The inner layer of opticalfibers 115 extends to the distal tip 130 of the catheter and terminatesat the distal emitter 120, while the outer layer of optical fibers 135terminates at the proximal emitter 140 within the balloon 150. In theinflated or partially inflated configuration shown in FIGS. 1-1B, theballoon 150 is inflated with liquid medium 160. As shown in FIG. 1B, across-sectional view along the plane demarcated by line B-B in FIG. 1,the liquid medium 160 is delivered into the balloon 150 via one or moreliquid medium ports 170 (see arrow in FIG. 1B). The liquid medium ports170 may also serve as a means for removing the liquid medium to modulatethe pressure within the balloon (for example, different pressuresrequired by different procedures) and to deflate the balloon 150.

The ability of liquid medium 160 to absorb light energy can degradeafter prolonged exposure to the light energy. Liquid medium 160 can beremoved from the balloon 150 through a separate set of liquid mediumports that act as liquid medium exit ports. Liquid medium exit portscan, for example, be configured to allow for the slow purgation orexchange of liquid medium 160 through an inner lumen in the catheter,while not significantly altering the overall pressure within the ballooncatheter itself.

In some embodiments, the catheter of the present disclosure includes oneor more additional lumens located near the inner lumen 110. For example,as shown in FIG. 1C, a cross-sectional view along the plane demarcatedby line C-C in FIG. 1, the catheter of the present disclosure caninclude a guidewire lumen 180 to allow a guidewire 190 to be insertedtherethrough, thereby facilitating the positioning of the distal end ofthe catheter within the vessel of the subject, as well as lumens for theinsertion of cameras, and cutting or ablation devices. Generally, thenumber of rows of optical fibers, emitters, and lumens located in thecatheter assembly and/or located concentrically around or adjacent tothe lumen and the number of optical fibers, emitters, and lumens in eachrow can vary by application and are not limited to the depictedconfigurations.

FIG. 2 is a representative longitudinal view of the distal end of laserballoon catheter 100 adjacent to a vascular obstruction or restriction210 within a vessel of a subject 220. The catheter 10 has been placed atthe desired location by sliding the catheter 100 over a guidewire 190through the guidewire lumen 180. To treat a subject having a vascularobstruction or restriction 210, the distal end of the laser ballooncatheter 100 is positioned adjacent to the vascular obstruction orrestriction 210. The balloon 150 is inflated to a desired pressure witha liquid medium 160 delivered from an inner lumen 110 through one ormore liquid medium ports 170 within the balloon 150. When the lasersystem is activated, light energy travels through one or more layers ofoptical fibers until the light energy is released from the proximallaser emitter 140.

For example, referring to FIG. 9, there is depicted an exemplary lasersystem 900 of the present disclosure. Laser system 900 includes a laserballoon catheter 100 coupled to a laser controller 950. Controller 950includes one or more computing devices programmed to control laser 230.Controller 950 may be internal or external to laser apparatus 920, suchas a laser generator. The laser apparatus 230 may include an excimerlaser or another suitable laser. In some embodiments, the laser 230produces light in the ultraviolet frequency range. In one embodiment,the laser 230 produces optical energy in pulses.

Laser 230 is connected with the proximal end of a laser energy deliverysystem, illustratively a laser catheter 100 via coupler 140. Lasercatheter 170 includes one or more transport members which receive laserenergy from laser 940 and transports the received laser energy from afirst, proximal end of laser energy catheter 100 towards a second,distal end of laser catheter 100. The distal end of catheter 100 may beinserted into a vessel or tissue of a human body 910. In someembodiments, system 900 employs a plurality of light guides as thetransport members, such as optical fibers, that guide laser light fromlaser 230 through catheter 100 toward a target area in human body 910.

Exemplary laser catheter devices or assemblies may include lasercatheters and/or laser catheters. Examples of laser catheters or lasercatheter are sold by The Spectranetics Corporation under the tradenamesELCA™ and Turbo Elite™ (each of which is used for coronary interventionor peripheral intervention, respectively, such as recanalizing occludedarteries, changing lesion morphology, and facilitating stent placement)and SLSII™ and GlideLight™ (which is used for surgically implanted leadremoval). The working (distal) end of a laser catheter typically has aplurality of laser emitters that emit energy and ablate the targetedtissue. The opposite (proximal) end of a laser catheter typically has afiber optic coupler 940 and an optional strain-relief member 930. Thefiber optic coupler 940 connects to a laser system or generator 930. Onesuch example of a laser system is the CVX-300 Excimer Laser System,which is also sold by the Spectranetics Corporation.

The laser controller 950 of FIG. 9 includes a non-transitorycomputer-readable medium (for example, memory) that includesinstructions that, when executed, cause one or more processors tocontrol laser 930 and/or other components of ablation system 900.Controller 950 includes one or more input devices to receive input froman operator. Exemplary input devices include keys, buttons, touchscreens, dials, switches, mouse, and trackballs which providing usercontrol of laser 930. Controller 950 further includes one or more outputdevices to provide feedback or information to an operator. Exemplaryoutput devices include a display, lights, audio devices which provideuser feedback or information.

FIG. 9 depicts the catheter 100 entering the leg, preferably through thefemoral artery, of the human body. As discussed above, it may bedesirable to treat either CAD or PAD. After entering the femoral artery,it the catheter 100 is intended to treat CAD, the catheter 170 will bedirected through the patient's vasculature system and to the coronaryarteries. Alternatively, if the catheter 100 is intended to treat PAD,the catheter 100 will be directed through the patient's vasculaturesystem and to the peripheral arteries, such as the vasculature below theknee, particularly the vasculature in the patient's legs and/or feet.

As discussed above, upon emitting the light into the liquid medium andthe liquid medium absorbing the light, a pressure wave is created in theliquid medium, which in turn generates a vapor bubble and a cavitationevent. The pressure waves penetrate and/or pass through the ballooncatheter 140, and the fluid movement associated with the formation andcollapse of the vapor bubble expands and then reduces the diameter ofthe balloon catheter. Referring again to FIG. 2, as the liquid medium160 absorbs the light energy, the pressure waves 240 (dotted lines)propagate through the liquid medium 160 and through the balloon 150.Upon passing through the balloon 150, the resultant energy of thepressure waves 240 transferred to the vascular obstruction orrestriction 210 and/or to the walls of the vessel 220. The transfer ofthe energy produced by the pressure waves 240 to the vascularobstruction or restriction 210 and/or to the walls of the vessel 220 issufficient to disrupt intraluminal as well as medial (within the tissuelayer of the vascular wall) vascular obstructions or restrictions (forexample, calcium deposits). The forces generated by the pressure waves240 can propagate radially, including in forward (such as, parallel tothe vessel), upward (such as, perpendicular to the vessel), and backward(such as, proximally) directions. Laser-induced pressure waves producedin this manner can also be used to increase vessel compliance prior toperforming another procedure, such as a traditional balloon angioplasty.

Laser-induced pressure waves generally have different characteristics incomparison to ultrasound. Ultrasound typically consists of periodicoscillations with limited bandwidth. Laser-induced pressure waves aresingle, mainly positive pressure pulses that are followed bycomparatively small tensile wave components. Ultrasound applies analternating high frequency load to tissue, with a frequency range ofseveral megahertz, and can thus lead to heating, tissue tears andcavitation at high amplitudes. The effect of laser-induced pressurewaves in comparison, however, largely involves radially directed energy,as described above, enabling the treatment of deep tissue as well asadjacent tissue with enhanced sensitivity.

Again, upon emitting the light into the liquid medium and the liquidmedium absorbing the light, a pressure wave in the liquid medium is notonly produced, but a vapor bubble is also created. The vapor bubblescreated within the balloon 150 of the balloon catheter or on theexterior of the balloon cause the balloon 150 to expand and contract.The fluid movement associated with the formation and collapse of thevapor bubble expands and then reduces the diameter of the balloon 150creating a hydraulic force that is also transferred to the vascularobstruction or restriction 210 and/or to the walls of the vessel 220 issufficient to disrupt intraluminal as well as medial (within the tissuelayer of the vascular wall) vascular obstruction or restrictions (forexample, calcium deposits).

Additionally or alternatively, the catheter of the present disclosurecan also be used to deliver one or more therapeutic agents to thevascular obstruction or restriction 210 and/or to the vascular tissuesof the vessel 220. The outwardly propagating pressure waves 240generated by the absorption of the light energy by the liquid medium 160and/or the rapid expansion and contraction of the balloon 150 candeliver one or more therapeutic agents that have been coated, forexample, on the outside of the balloon 150. When the balloon 150 isbrought in contact with the desired target (for example, a vascularobstruction or restriction 210 and/or the vascular tissues of the vessel220), the propagation of the pressure waves 240 through the balloon 150and/or the expansion and contraction of the balloon 150 causes thetherapeutic agent to become detached from the balloon 150 and bedelivered to or embedded in the desired target. Additionally, undersuitable therapeutic parameters, the pressure waves 240 may create smallspaces within the vascular obstruction or restriction 210 and/or withinthe vascular tissues of the vessel 220, which may enhance thepenetration of the therapeutic agent into the vascular obstruction orrestriction 210 or the vascular tissue of the vessel 220. Energy fromthe pressure waves 240 may also increase the kinetic energy of themolecules making up the therapeutic agents, which may further enhancethe delivery and penetration of the therapeutic agent into the targettissue.

The therapeutic agents of the present disclosure can be chosen basedupon functional characteristics, including, but not necessarily limitedto, the ability to inhibit restenosis, mitosis or cellularproliferation. For example, a therapeutic agent can be a taxane,including paclitaxel, docetaxel, protaxel, DHA-paclitaxel,PG-paclitaxel, docosahexaenoic acid (DHA), or any combinations orderivatives thereof capable of inhibiting mitosis or cellularproliferation. In some cases, the presence of a mitotic inhibitorprevents restenosis that may occur in the absence of the inhibitor.Other examples of therapeutic agents include rapamycin (for example,sirolimus) or a derivative of rapamycin (for example, everolimus), orany combinations or derivatives thereof. Additionally or alternatively,specific inhibitors of neovascularization such as thalidomide, statinssuch as atorvastatin, cerivastatin, fluvastatin, or anti-inflammatorydrugs like corticoids or lipophilic derivatives of corticoids such asbetamethasone diproprionate or dexa-methasone-21-palmitate are examplesof oxidation-insensitive drugs that can be used with the laser ablationcatheters of the present disclosure. Various therapeutic agents may beapplied or combined if different pharmacological actions are required orefficacy or tolerance is to be improved.

The therapeutic agents can also be combined with various adjuvants andexcipients to enhance efficacy or delivery of the therapeutic agents.For example, the therapeutic agents can be combined with lipophilicantioxidant such as nordihydroguaiaretic acid, resveratrol and propylgallate to enhance the adhesion of the therapeutic to, for example, aballoon catheter. In some cases, the combination of a therapeutic agentsuch as paclitaxel and a lipophilic antioxidant such asnordihydroguaiaretic acid can be applied to a balloon catheter withoutthe need for additional polymers (such as, polymer-free).

The ability of the catheter of the present disclosure to generatepressure waves 240 for treating a vascular obstruction or restriction210 in a subject involves the suitable coupling of the light system 240and the liquid medium 160. Any wavelength of light can be used,including but not limited to, laser light, visible light, ultravioletlight and infrared light, as long as the light being emitted is coupledwith a liquid medium capable of absorbing the light and producingpressure waves. Additionally, any liquid medium can be used, as long asthe liquid medium is coupled with a light source that emits light at asuitable wavelength such that the liquid absorbs the light and producesresultant pressure waves. In some cases, the liquid medium can becontrast medium (for example, iodine-containing contrast medium orgadolinium contrast medium) and/or the liquid medium can be a contrastsolution comprising a biocompatible fluid (for example, saline) in whicha contrast dye(s) or particle(s) have been mixed at variousconcentrations.

The force amplitude generated by the laser-induced pressure waves 240depends in part on the degree of absorption of the light energy by theliquid medium 160. Generally, the greater the absorption of the lightenergy by the liquid medium 160, the greater the force generated by thepressure waves 240. For example, an excimer laser typically emits laserlight at a wavelength of about 308 nanometers at pulse durations betweenabout 120 nanoseconds and about 140 nanoseconds, at frequencies betweenabout 25 pulses per second to about 80 pulses per second, and with atotal energy output between about 30 to about 80 millijoules permillimeter squared (mJ/mm²). In some cases, however, total energy outputof a laser light system can range from greater than 0 to about 300mJ/mm². When emitted within contrast medium, such as iodine-containingcontrast medium or gadolinium contrast medium, there will be a very highdegree of absorption by the contrast medium, thus creating pressurewaves with sufficient force to treat a vascular obstruction orrestriction in a subject.

Light energy can be emitted at any suitable wavelength capable ofgenerating pressure waves. Light energy can be emitted between about 1nanometer and about 1 millimeter. In some cases, light can be emittedfrom about 10 nanometers to about 5000 nanometers. In some cases, lightcan be emitted from about 100 nanometers to about 1000 nanometers. Insome cases, light can be emitted from about 250 nanometers to about 750nanometers. In some cases, light can be emitted from about 300nanometers to about 600 nanometers. In still other cases, light can beemitted from about 300 nanometers to about 350 nanometers.

Light energy can be emitted at any suitable pulse duration capable ofgenerating pressure waves. In some cases, light can be emitted at pulsedurations between about 1 nanosecond to about 1 second. In some cases,light can be emitted at pulse durations between about 10 nanoseconds toabout 500 nanoseconds. In some cases, light can be emitted at pulsedurations between about 100 nanoseconds to about 150 nanoseconds. Instill other cases, light can be emitted at pulse durations between about120 nanoseconds and about 140 nanoseconds.

Light energy can be emitted at any suitable pulse repetition frequency(PRF), or pulses per second, capable of generating pressure waves thatpropagate through the balloon catheter and the surrounding vasculature.In some cases, light can be pulsed at a frequency of between about 1pulse to about 500 pulses per second. In some cases, light can be pulsedat a frequency of between about 10 pulses to about 250 pulses persecond. In some cases, light can be pulsed at a frequency of betweenabout 10 pulses to about 150 pulses per second. In some cases, light canbe pulsed at a frequency of between about 10 pulses to about 100 pulsesper second. In other cases, light can be pulsed at a frequency ofbetween about 50 pulses to about 150 pulses per second. In other cases,light can be pulsed at a frequency of between about 50 pulses to about100 pulses per second. In still other cases, light can be pulsed at afrequency of between about 25 pulses to about 80 pulses per second.

The total number of pulses administered during a particular treatmentperiod depends on a variety of factors, including patientcharacteristics, the type of condition being treated, and the specificcharacteristics of the vascular obstruction or restriction, as one ofordinary skill in the art would readily appreciate based on the presentdisclosure. In some cases, the total number of pulses administeredduring a treatment period can range from a single pulse to any number ofpulses generated in a 10 second treatment period, a 15 second treatmentperiod, a 20 second treatment period, a 25 second treatment period, a 30second treatment period, up to a 1 minute treatment period. Treatmentperiods can be repeated depending on the extent of the vascularobstruction or restriction remaining after initial treatment.

The degree of force generated by the pressure waves 240 can be modulatedby using lasers that produces laser light energy at differentwavelengths and at different pulse durations, as would be appreciated byone of ordinary skill in the art based on the present disclosure. Forexample, different degrees of force may be required to break apart avascular obstruction or restriction, as compared to the degree of forcerequired to deliver a therapeutic agent to vascular tissue. In someembodiments, a laser having a holmium source, referred a Holmium laser,can emit laser light energy at a wavelength of about 2,100 nanometers(nm) and can be coupled with various light absorbing materials,including an aqueous or saline-based medium, to treat a vascularobstruction or restriction in a subject.

Several other additional sources of laser light energy can be pairedwith corresponding light absorbing materials to generate pressure wavesto treat a vascular obstruction or restriction. For example, YAG crystallasers can produce wavelengths of infrared light, which is highlyabsorptive in aqueous solutions. Aqueous solutions can be used as lightabsorbing material or medium to generate pressure waves. Aqueoussolutions include, but are not limited to, saline, dextrose,radio-opaque contrast, lactated ringer's, and electrolyte solutions. Insome cases, YAG wavelengths can be doubled to generate visible spectrumlight of 532 nm wavelength. Materials or medium capable of absorbinglight of this wavelength include, but are not limited to, goldnanospheres, nitrite solutions, potassium permanganate solutions, coppersalts, aluminum solutions, aluminon, ammonia salts, and dyes such ashemotoxylin and propidium iodide. Light absorbing materials such asthese can be part of a solution, such as an aqueous solution asdescribed above, and/or they can be applied as coatings on varioussurfaces within a device.

In some embodiments, a Holmium YAG laser can emit laser light energy ata wavelength of about 2,120 nm and can be coupled with various lightabsorbing materials, including an aqueous or saline-based medium, totreat a vascular obstruction or restriction in a subject. In someembodiments, a thulium laser, such as a Thulium YAG laser, can emitlaser light energy at a wavelength of about 2,013 nm and can be coupledwith various light absorbing materials, including an aqueous orsaline-based medium, to treat a vascular obstruction or restriction in asubject. In some embodiments, a thulium laser, such as a Thulium Fiberlaser, can emit laser light energy at a wavelength of about 1,908 nm andcan be coupled with various light absorbing materials, including anaqueous or saline-based medium, to treat a vascular obstruction orrestriction in a subject. In some embodiments, an Nd-YAG laser can emitlaser light energy at a wavelength of about 1,064 nm and can be coupledwith various light absorbing materials to treat a vascular obstructionor restriction in a subject. In some embodiments, a doubled YAG lasercan emit laser light energy at a wavelength of about 532 nm and can becoupled with various light absorbing materials to treat a vascularobstruction or restriction in a subject. In some embodiments, analternative band YAG laser can emit laser light energy at a wavelengthof about 1,319 nm and can be coupled with various light absorbingmaterials to treat a vascular obstruction or restriction in a subject.In still other embodiments, an Er-YAG laser can emit laser light energyat a wavelength of about 2,940 nm and can be coupled with various lightabsorbing materials to treat a vascular obstruction or restriction in asubject.

Carbon dioxide (CO₂) lasers can emit infrared light that is highlyabsorptive in aqueous solutions. CO₂ lasers are common surgical lasersand are highly absorptive in tissues due to their high water content.Light absorbing materials that can be coupled with CO₂ lasers that emitinfrared light, such as light emitted at a 10.6 micron wavelength, togenerate pressure waves include, but are not limited to, aqueoussolutions such as saline, dextrose, radio-opaque contrast, lactatedringer's, and electrolyte solutions.

Nitrogen lasers can be used to produce low frequency, high energy laserpulses. Nitrogen lasers can emit light in the UV spectrum can emit laserlight energy at a wavelength of about 337 nm and can be coupled withvarious light absorbing materials to generate pressure waves, includingbut not limited to, radio-opaque contrast as well as metals and oxidessuch as aluminum, silver, gold, copper, nickel, cerium, zinc, titanium,and dyes such as hydroxycoumarin and aminocoumarin.

Other medically useful lasers that can be used to generate a pressurewave to treat a vascular obstruction or restriction include Ti-Sapphirelasers, which can emit laser light energy at wavelengths of about 800nm; Ruby lasers, which can emit laser light energy at wavelengths ofabout 694 nm; and Alexandrite lasers, which can emit laser light energyat about 755 nm. These medical lasers emit laser light energy in thenear infrared light spectrum, and can be used for pressure wavegeneration. Light absorbing material or medium that can be coupled withthese laser include, but are not limited to, dyes and colorants whichcould be used in solution, suspension, or coating on another material orsurface within a device. Various materials capable of absorbing laserlight energy in these wavelengths include aqueous copper, copper salts,and cupric sulfate, and materials such as fluorophores that are used influorescent microscopy (for example, methylene blue).

Dye lasers can also be used to generate pressure waves to treat avascular occlusion. In some cases, dye lasers can be tuned to output aspecific wavelength of light in the visible spectrum, which can allowfor the optimization of the laser for a certain light absorbingmaterial, as an alternative or in addition to, using a material which ishighly absorptive of a specific wavelength of light. In this way, thelight absorbing material can be any of the previously mentionedmaterials, as well as dyes, colorants, and visible light chromophores.

The force generated by the pressure waves 240 can also obviate the needto inflate the balloon 150 to the high pressures typically required totreat effectively a subject during angioplasty or other balloonprocedures (for example, 14-16 atmospheres). In some cases, the balloon150 of the present disclosure can be inflated with liquid medium 160 topressures greater than 0 atmospheres to about 20.0 atmospheres. In somecases, the balloon 150 of the present disclosure can be inflated withliquid medium 160 to pressures between about 1.0 atmosphere to about10.0 atmospheres. In other cases, the balloon 150 of the presentdisclosure can be inflated with liquid medium 160 to about 0.5, 1.5,2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5,9.0, 9.5, 10.0, 10.5, 11.0, 11.5, 12.0, 12.5, 13.0, 13.5, 14.0, 14.5,15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, or 20.0atmospheres. The use of dilation balloon assemblies 150 at low pressurescan reduce the potential for damaging healthy vascular tissue during aprocedure, and can facilitate the treatment of a greater range and typesof vascular obstruction or restrictions.

In contrast to U.S. application Ser. No. 13/800,214, which published asUS20140277002A1, and disclosed inflating a cutting or scoring balloon,followed by the use of pulsed laser light to cause the cutting orscoring elements to vibrate and assist in the cracking or abrading ofthe surrounding plaque, the balloon catheter of the present disclosureuses lower pressures, which may improve clinical outcomes. FIG. 3A is arepresentative perspective view of the distal end a catheter havingmultiple, telescopically extending, concentric proximal laser emitters300, 310, 320 coupled to one or more laser catheters. Each of theconcentric proximal laser emitters 300, 310, 320 is the terminationpoint of an optical fiber layer that lies within a balloon catheter. Bybeing positioned within the balloon catheter, the transmitted laserlight energy can interact with the absorptive liquid medium in severallocations along the distal end of the laser ablation catheter, therebyproviding the ability to treat a greater range and types of vascularobstruction or restrictions. For example, the concentric proximal laseremitter 300 can be activated to treat a more proximally located vascularobstruction or restriction (with reference to the balloon catheter),while the concentric proximal laser emitter 320 can be activated totreat a more distally located vascular obstruction or restriction.Concentric proximal laser emitter 310 can be used to treat a vascularobstruction or restriction located somewhere in between. FIG. 3B is arepresentative perspective view of the distal end a catheter havingmultiple single-fiber proximal laser emitters 330, 340, in lieu ofconcentric proximal laser emitters. In any of the aforementionedconfigurations, the liquid medium ports may be arranged in one or morelocations along each, or all, of the optical fiber layers.

FIG. 3C is a cross-sectional view (through plane C in FIG. 3A) of thedistal end of a catheter showing multiple layers of optical fibers thatterminate at proximal laser emitters 300, 310, 320, which are disposedwithin the balloon catheter 350. The catheter of FIG. 3C also includes aguidewire lumen to allow a guidewire 390 to be inserted therethrough,thereby facilitating the positioning of the distal end of the catheterwithin the vessel of a subject.

The multiple proximal laser emitters in FIGS. 3A and 3B can be activatedin any sequence during a procedure, including individually orsimultaneously with each other, thereby providing a greater range oftreatment options. The number, size, and/or location of the emitters canbe varied to customize the delivery of the laser light energy into theabsorptive liquid medium. For example, multiple proximal laser emittersmay decrease the overall pressure required in the balloon to have thesame effect as that of a catheter with one or no proximal emitters. Theemitters can be permanently fixed within a balloon catheter at thedistal end of the catheter or they can be inserted any time during aprocedure. Various other numbers and arrangements of proximal laseremitters can be used, depending on the characteristics of the vascularobstruction or restriction and the individual subject being treated, ascan be appreciated by one of ordinary skill in the art based on thepresent disclosure. For example, the proximal laser emitters 300, 310,320 need not be in multiple layers, but could be in a single layer witha single physical construction to create such emission.

FIGS. 4A-4C are representative perspective views of the distal end of alaser balloon catheter with a translational proximal (such as, sliding)laser emitter 400 in three different positions within a ballooncatheter. The translational proximal laser emitter 400 is thetermination point of a layer of optical fibers configured to betranslated longitudinally within the balloon catheter along the axis ofthe distal end of the catheter. This facilitates the use of the entirearea of the balloon catheter during a procedure, or it facilitates theuse of only a specific area of the balloon catheter during a procedure.FIG. 4A depicts the translational proximal laser emitter 400 in a moreproximal position with reference to the balloon catheter; FIG. 4Bdepicts the translational proximal laser emitter 400 in a medialposition with reference to the balloon catheter; and FIG. 4C depicts thetranslational proximal laser emitter 400 in a more distal position withreference to the balloon catheter. The ability to position thetranslational proximal laser emitter 400 before, during, or after aprocedure provides for the treatment of a greater range and types ofvascular obstruction or restrictions in a subject. In some cases,embodiments of the catheters described in FIGS. 3A and 3B may alsoincorporate the translational positioning of embodiments of thecatheters described in FIGS. 4A-4C such that they can slide with respectto each other along the distal end of the catheter.

In some embodiments, catheters of the present disclosure can include alayer of optical fibers than can be translated longitudinally in and outof the balloon catheter along the axis of the distal end of thecatheter. The balloon catheter can be coupled to an outer catheter onthe catheter, and in some cases, the one or more emitters can betranslated longitudinally to the distal tip of the catheter distal to(and externally from) the balloon catheter to, for example, emit lightto ablate a portion of a vascular occlusion. In some embodiments, theone or more emitters can then be translated proximally into the ballooncatheter, where the one or more emitters can be passed through a valveor opening in the catheter coupled to the balloon catheter such that theemitters can now emit light into a liquid medium contained within theballoon catheter to produce pressure waves to treat a vascular occlusionand/or deliver a therapeutic agent. Such embodiments can enable the useof only a single layer of optical fibers and/or emitters to perform bothablation and pressure wave propagation procedures.

The catheters of the present disclosure may be configured as separatecomponents; for example, laser ablation catheter can be separate fromthe balloon catheter, and the laser ablation catheter may be insertedinto the balloon catheter prior to the commencement of a procedure. Thecatheters of the present disclosure may also include one or moreradiopaque markers positioned on the balloon catheter (for example,marking the proximal and distal ends of the balloon catheter) in orderto assist with the placement of the distal end of the catheter at thedesired location within the subject's vessel prior to the commencementof a procedure. The catheters of the present disclosure may also includeone or more radiopaque markers positioned at and/or near the emitters inorder to assist with the placement of the emitters within the ballooncatheter, for example, such that the emitters are positioned adjacent toa vascular obstruction or restriction prior to the commencement of aprocedure. Radiopaque markers can be made of any suitable materialsknown in the art, including but not limited to, platinum, iridium, andalloys thereof.

Referring to the flow chart in FIG. 5, the present disclosure includes amethod for treating a subject with a vascular obstruction or restriction500 using embodiments of the catheter described herein. Although it isnot illustrated in FIG. 5, it may be desirable to use a laser catheterto ablate at least a portion of the vascular occlusion in the vessel ofthe subject prior to performing the method set forth in FIG. 5 and/orusing the a laser catheter to ablate at least a portion of the vascularocclusion in the vessel prior to and/or subsequent to performing any ofthe steps set forth in FIG. 5. The method 500 in FIG. 5 includeslocating a vascular obstruction or restriction in the vessel of asubject 510. The next step, which is optional, includes locating aguidewire at the occlusion and/or inserting a guidewire through theocclusion 515. Thereafter, any of the embodiments of the catheters 100,1000 described herein may be slid over the guidewire and into thevasculature such that the balloon catheter, which is coupled to thecatheter 100, 1000, is positioned adjacent to the vascular obstructionor restriction 520. As discussed herein, the laser emitters within theballoon catheter may be fixed or slidable with respect to the ballooncatheter. For example, if the laser emitters are included with the lasercatheter, which is slidable within the catheter and balloon catheter ofthe balloon catheter, the emitters may be positioned (and subsequentlyre-positioned) anywhere along the length of the balloon at a desiredlocation. Additionally or alternatively, the method 500 includesinflating the balloon catheter by delivering the liquid medium (forexample, contrast medium) from the inner lumen of the catheter throughone or more liquid medium ports and into the balloon catheter 540. Insome cases, the method 500 includes activating at least one laseremitter enclosed within the balloon catheter to emit and send pulses oflaser light energy into and/or to react with the liquid medium toproduce propagating pressure waves and disrupt a portion of the vascularocclusion 550. In some cases, the method 500 includes activating atleast one laser emitter enclosed within the balloon catheter to emit andsend pulses of laser light energy into and/or to react with the liquidmedium to produce propagating pressure waves to deliver a therapeuticagent to the vascular obstruction or restriction and/or the vasculartissue near the obstruction or restriction 560. Activating a proximallaser emitter to disrupt a portion of a vascular obstruction orrestriction and/or to deliver a therapeutic agent can be performed inany sequence, if at all, as part of the method 500. For example, step550 could be performed without performing step 560, step 560 could beperformed without performing step 550, step 550 could be performedserially while performing step 560, such that step 550 is performedfirstly and step 560 is performed secondly, step 550 could be performedserially while performing step 560, such that step 560 is performedfirstly and step 550 is performed secondly, or steps 550 and 560 couldbe performed in parallel. Upon completing step 550 and/or step 560, theballoon catheter can optionally be repositioned within the vasculatureand adjacent another portion thereof. Similarly, upon completing step550 and/or step 560, the emitter(s) can optionally be repositionedwithin the balloon catheter. Either or both the balloon catheter can berepositioned within the vasculature or the emitter(s) within the ballooncatheter can be repositioned. The method 500 also includes ending theprocedure when the desired therapeutic outcome is obtained, or repeatingany of 510 through 560 as may be necessary to treat a subject having avascular obstruction or restriction. Furthermore, if step 560 is notperformed in the method depicted in FIG. 5, a drug eluting (coated)balloon (DEB or DCB) catheter may be used to deliver drugs to theremnants of the vascular occlusion. Disrupting the vascular occlusionwith the pressure waves prior to utilizing a DEB may increase theeffectiveness of the drugs being applied to the vascular occlusionbecause to the pressure waves disrupt the intraluminal as well as medial(within the tissue layer of the vascular wall) vascular obstruction orrestrictions (for example, calcium deposits), thereby creating a pathwayfor the drug to enter the intraluminal and medial portions of thevasculature and/or vascular occlusion.

Although the method illustrated in FIG. 5 depicts step 520, whichincludes positioning the balloon catheter adjacent the vascularocclusion, being performed prior to step 525, which includes positioningthe emitters within the balloon catheter at a desired location, step 525may be performed after or in parallel with step 520. Additionally,although the method illustrated in FIG. 5 depicts step 520 and step 525as occurring prior to step 540, which includes inflating the ballooncatheter with liquid medium, step 540 may be performed prior to or inparallel with one or both of step 520 or step 525. That is, steps 520,525 and 540 may be performed in any order.

Additionally or alternatively, methods of the present disclosure alsoinclude activating at least one proximal laser emitter enclosed withinthe balloon catheter to emit pulses of laser light energy to react withand/or to react with the liquid medium and propagating pressure waves toassist in stent deployment. Cavitation bubbles generated by pulsinglaser light energy, which reacts with the liquid medium and can assistin seating or expanding the stent to its full diameter as part of amedical procedure.

Although a large portion of this disclosure includes a discussion oflaser ablation catheters used in conjunction with a balloon catheter,catheters having mechanical cutting instruments may also be used. Lasercatheters typically transmit laser energy through emitters housed in arelatively flexible tubular catheter inserted into a body lumen, such asa blood vessel, ureter, fallopian tube, cerebral artery and the like toremove obstruction or restrictions in the lumen. Catheters used forlaser angioplasty and other procedures may have a central passageway ortube which receives a guidewire inserted into the body lumen (forexample, vascular system) prior to catheter introduction. The guidewirefacilitates the advancement and placement of the catheter to theselected portion(s) of the body lumen for laser ablation of tissue.

Examples of laser catheters are sold by The Spectranetics Corporationunder the tradenames ELCA™ and Turbo Elite™ (each of which is used forcoronary or peripheral intervention or catheterization such asrecanalizing occluded arteries, changing lesion morphology, andfacilitating stent placement) and SLSII™ and GlideLight™ (which is usedfor surgically implanted lead removal). The working (distal) end of alaser catheter typically has a plurality of emitters that emit energyand ablate the targeted tissue. The opposite (proximal) end of a lasercatheter typically has a coupler, which connects to a laser system orgenerator. One such example of a laser system is the CVX-300 ExcimerLaser System, which is also sold by The Spectranetics Corporation, andis illustrated in FIG. 9, which has been previously discussed herein.

Traditional balloon catheter typically includes a two-catheterconstruction such that an inner catheter is disposed within an outercatheter, and the inner catheter extends beyond the distal end of theouter catheter. A balloon is coupled to the inner catheter and outercatheter. Incorporating a laser ablation catheter between the innercatheter and outer catheter of a balloon catheter, however, increasesthe overall size and diameter of the balloon catheter, therebypotentially limiting the ability of the balloon catheter to reach andtreat smaller sized vessels, such as peripheral arteries below theknees, particularly those arteries located within the feet. It is,therefore, desirable to reduce the overall size and diameter of theballoon catheter, including the size and diameter of the catheter(s)and/or the balloon. Reducing the overall size and diameter of theballoon catheter will, therefore, increase the balloon catheter'sability to reach and treat smaller sized peripheral arteries and othersmaller sized vasculature.

One potential solution for reducing the overall size and diameter of theballoon catheter is to remove the inner catheter, which will allow theballoon and outer catheter (now just one catheter) to be sized smaller.Removing the inner catheter, however, removes (a) the lumen throughwhich the guidewire travelled and (b) the component to which the balloonwas coupled and (c) the ability to seal the inflation medium used toinflate the balloon. What is, therefore, needed is a means for couplingthe distal portion of the balloon while allowing a guidewire to passtherethrough and for providing a seal with the guidewire uponintroduction of the inflation medium into the balloon.

Referring to FIGS. 10 and 10A and 10B, there is depicted the distal endof an alternative system for treating an obstruction or restrictionwithin vasculature of a subject that includes such a means and omits astationary inner catheter, which is typically included within atraditional balloon catheter. The system comprises a catheter 1000 and alaser catheter 1020 insertable and slidable within the catheter 1000.The catheter 1000 includes a catheter 1010 with a lumen (not shown)extending form its proximal end to its distal end, a tip 1030, and aballoon 1050 coupled to the tip 1030 and a distal portion of thecatheter 1010. The catheter 1000 does not include a catheter (with alumen) extending between the distal end of the catheter 1010 and theproximal end of the tip 1030 within the balloon. The system furthercomprises a laser catheter 1020 comprising a proximal portion, distalportion 1025, which may be protected by a smooth outer metal band, oneor more emitters disposed within the laser catheter 1020, and at leastone energy source (not shown) coupled to the one or more emitters andexposed at the distal portion 1025 of the laser catheter 1020 within theballoon 1050. The at least one or more emitters extend from the proximalportion of the laser catheter 1020, which is coupled to a lasergenerator, as discussed with respect to FIG. 9 hereinbefore,

Referring to FIGS. 11, 11A, and 11B, the tip 1030 includes a proximalend 1034, a distal end 1036 and a lumen 1038 extending therethrough fromits proximal end 1034 to its distal end 1036. The tip 1030 includes avalve that seals the intersection of the tip 1030 and the guidewire 1040as the guidewire 1040 passes through the guidewire lumen 1038. Oneexample of a valve is that which is depicted in FIGS. 11, 11A, and 11Bwhich illustrate a flange 1046 that is disposed at and/or toward theproximal end 1034 of the tip 1030.

Referring back to FIGS. 10, 10A, and 10B, the balloon 1050 is coupled tothe distal end of the catheter 1010 and the tip 1050. Upon introducingthe guidewire 1040 through the lumen of the catheter 1010 and into theguidewire lumen 1038 of the tip, the catheter 1010 and tip 1030 areslidably coupled such that the catheter 1010 and tip 1030 can slide overthe guidewire 1040, as depicted in FIG. 11A. As illustrated in thisfigure, there is a gap (or opening) caused by the guidewire lumen 1038between the flange 1046 and the guidewire 1040. If the gap is maintainedduring introduction of the inflation medium into the balloon 1050, theinflation medium would travel through the guidewire lumen 1038 and intothe patient's vasculature, which may be undesirable. The flange 1046,which may include a tapered portion 1042 that tapers from the tip'sdistal end toward its proximal end, is configured to radially collapseupon introduction of the inflation medium into the balloon 1050 due tothe increased fluid pressure on the flange 1046. The increased fluidpressure on the flange 1046 actuates the flange 1046 and moves itradially inward toward the guidewire lumen 1038 such that the gapbetween flange 1046 and the guidewire 1040 closes, thereby creating aseal between the between flange 1046 and the guidewire 1040, as depictedin FIG. 11B. The reduced thickness of the tapered portion 1042 of theflange 1046 as the flange 1046 tapers radially inward towards theguidewire lumen 1038 as the flange 1046 progresses from the distal end1036 toward the proximal portion 1034 increases the flange's ability toflex upon exposure to the pressure created upon introduction of theinflation fluid. Upon removal of the inflation medium from the balloon1050, the pressure within the balloon 1050 decreases, the pressure onthe flange 1046 decreases, and the flange 1046 naturally retracts to itsoriginal position as depicted in FIG. 11A, thereby reestablishing thegap between the tip 1030 and the guidewire 1040 so that the twocomponents may slide with respect to one another. Accordingly, theflange 1046 acts as a sealable valve within the tip 1030, and the flange1046 is actuated with the introduction and removal of the inflationmedium into and from the balloon 1050.

Although the tapered portion 1042 illustrated in FIGS. 11A and 11Btapers from the tip's distal end toward its proximal end, the directionof the taper may be reversed such that the tapered portion tapers fromthe tip's proximal end toward its distal end. Additionally, the flange1046 may taper towards any portion along its length such that a portionof the flange is thinner at one or more locations along its length incomparison to other locations along its length. Accordingly, upon anincreased fluid pressure being imparted on the flange 1046, thinnerportion of the flange 1046 actuates and moves radially inward toward theguidewire lumen 1038 such that the gap between flange 1046 and theguidewire 1040 closes, thereby creating a seal between the betweenflange 1046 and the guidewire 1040.

FIGS. 10, 10A, 10B, 11, 11A, and 11B, do not illustrate an inflationlumen through which the inflation medium is introduced and removed fromthe balloon. Nevertheless, the catheter 1010 may also include a separateinflation lumen (not shown) integrally located within the structure ofthe catheter 1010 itself or the inflation medium may be introduced intothe balloon 1050 through an opening (or gap) between the laser catheter1020 and the catheter 1010. For the purposes of this disclosure, theinflation shall include both the separate inflation lumen integrallylocated within the structure of the catheter 1010 itself and an opening(or gap) between the laser catheter 1020 and the catheter 1010.

Referring again to FIGS. 11, 11A, and 11B the tip 1030 may beconstructed from any type of compressible or compliant biopolymers, suchas silicones or flouro-polymers, compliant adhesives, etc. Theconfiguration of the tip 1030 depicted in these figures includes anexterior wall 1044 and a flange 1046 disposed radially therein, tocreate a gap therebetween for the inflation medium to enter and actuatethe flange 1046. The flange is also depicted as being disposed towardthe proximal end 1024 of the tip 130, which itself is depicted astubular, and its distal end has an inward taper that tapers distallyfrom the exterior wall 1044 towards the guidewire lumen 1038. Althoughthe tip 1030 is depicted as including particular components and shapes,the present disclosure shall include other shapes and components knownto one of skill in the art. Moreover, the tip may alternatively includea self-sealing tube constructed of any type of compressible or compliantbiopolymers, such as silicones or flouro-polymers, compliant adhesives,etc. For example, the tip may include a tube that has a lumen passingtherethrough such that upon insertion of a guidewire, the lumen expands,and upon removable of the guidewire, the lumen contracts, therebyappearing as a slit.

As discussed above, omitting a stationary inner catheter form atraditional balloon catheter and including a tip distally disposed fromthe catheter of the balloon catheter has the advantage of reducing thesize of the balloon, and hence smaller sized balloons can enter smallervessels, particularly peripheral arteries below the knee. Additionally,when a traditional balloon catheter is inflated with liquid, such assaline (and possibly with a contrast medium), air may become trapped andunable to escape from the balloon. The tip 1030, particularly theactuation of the flange 1046, which acts as sealable valve within thetip 1030, allows the air initially included within the balloon to escapeduring inflation, thereby potentially increasing the balloon's ease ofuse, as well as its effectiveness. For example, during preparation ofthe balloon, it is common to deflate the balloon, thereby extracting asmuch air as possible, prior to use. However, it is impractical to removeall of the air during such extraction process. The tip 1030, therebyallows a user to remove more or all air from the balloon duringpreparation. Additionally, it may not be necessary to deflate theballoon and remove any air prior to use, because the air is allowed toescape during inflation with the liquid.

Continuing to FIGS. 10, 10A, 10B, 11, 11A, and 11B, the tip 1030 mayinclude one or more openings 1032 through its exterior wall 1044. Theopenings 1032 allow the inflation liquid to reach the flange 1046 notonly from the gap between the flange 1046 and the exterior wall 1044 atthe proximal end 1034 of the tip 1030 but also at a location distal theproximal end 1034 of the tip 1030. Allowing allow the inflation liquidto reach the flange 1046 at or toward its distal portion, potentiallyincreases the likelihood and effectiveness of actuating the flange 1046.Although the tip 1030 is illustrated as having a tubular section 1037from its proximal end 1034 and a tapered section 1035 from the end ofits tubular section toward the tips distal end 1036, the scope of thisdisclosure shall include other shapes for the tip.

As discussed herein, as the laser light is emitted from the emitter(s),the light interacts with the liquid medium, and the liquid mediumabsorbs the light energy, thereby creating vapor bubbles within theballoon catheter. The openings 1032 within the tip 1030 may reduce thesize of the bubble formed within the balloon catheter and/or reduce thelikelihood that the bubble will expand toward the distal end of theballoon catheter.

Additionally, although FIGS. 10, 10A, 10B, 11, 11A, and 11B include atip 1030 included within a balloon catheter that omits a stationaryinner catheter, the scope of this disclosure includes utilizing a tip1030 in a balloon catheter that includes an inner catheter in additionto an outer catheter to which the proximal end of the balloon isattached.

As discussed above, transmitting pulses of laser light energy from anemitter into a liquid medium generates a plurality of propagatinglaser-induced pressure waves that cause the balloon catheter, whichsurrounds the liquid medium, to engage and disrupt at least a portion ofthe vascular obstruction or restriction. The catheter, which the ballooncatheter, and the balloon itself, may each include a guidewire lumenthrough which a guidewire can pass and cross the occlusion. It may alsobe desirable to excite and vibrate the guidewire to increase theguidewire's ability to pierce and cross the occlusion. Accordingly, thepresent disclosure also contemplates directing the laser-inducedpressure wave and/or cavitation event toward the guidewire lumen and/orguidewire such that the pressure waves excite and vibrate the guidewire.

Referring to FIG. 6, there is depicted an end view of the distal end ofa catheter 600 within a balloon catheter 650 in a partially inflatedconfiguration, according to one embodiment of the present disclosure. Asshown, the distal end of the catheter 600 includes one or more emitters615 arranged circumferentially around an inner inflation lumen 610 andan inner guidewire lumen 680. The emitters 615 extend to the distal tipof the catheter and terminate at the distal emitter 620 within theballoon catheter 650.

In the inflated or partially inflated configuration shown in FIG. 6, theballoon catheter 650 is inflated with liquid medium 660. The liquidmedium 660 is delivered into the balloon catheter 650 via one or moreliquid medium ports 670. The liquid medium port(s) 670 may also serve asa means for removing the liquid medium to modulate the pressure withinthe balloon (for example, different pressures required by differentprocedures) and to deflate the balloon catheter 650.

The ability of liquid medium 660 to absorb light energy can degradeafter prolonged exposure to the light energy. Liquid medium 660 can beremoved from the balloon catheter 650 through a separate set of liquidmedium ports that act as liquid medium exit ports. Liquid medium exitports can, for example, be configured to allow for the slow purgation orexchange of liquid medium 660 through an inner lumen in the catheter,while not significantly altering the overall pressure within the ballooncatheter itself.

FIGS. 6 and 6A depict the inner inflation lumen 610 and the innerguidewire lumen 680 in a radially offset configuration with respect tothe longitudinal axis of the catheter 600. That is, the inflation lumen610 and the inner guidewire lumen 680 are eccentrically oriented withrespect to one another and with respect to the longitudinal axis of thecatheter 600. Either the inner inflation lumen 610 or the innerguidewire lumen 680, however, may be concentrically located with respectto the longitudinal axis of the catheter 600.

Additionally, FIG. 6A depicts the inflation lumen 610 terminating withinthe catheter 600, and the guidewire lumen 680 extending through thedistal tip 685 of the catheter 600. The inflation lumen 610, however,may alternatively extend through the distal tip of the catheter suchthat the liquid medium not only enters the balloon catheter 650 throughthe one or more liquid medium ports 670, but the liquid medium can alsoenter the balloon catheter 650 though the opening of the inflation lumen610 through the distal tip 685 of the catheter 600, or the liquid mediumcan also enter the patient's vasculature though the opening of theinflation lumen 610 through the distal tip 685 of the catheter 600.Furthermore, although FIG. 6 illustrates only one liquid medium port670, the catheter 600 may include a plurality of liquid medium portsfluidly coupled to the inflation lumen 610 and disposed concentricallyaround the perimeter of the laser catheter 600 to inflate the ballooncatheter 650 with the liquid medium 660.

Continuing to refer to FIG. 6A, in addition to having a plurality ofemitters 615, an inflation lumen 610, one or more liquid medium ports670, and a guidewire lumen 680, the catheter 600 may also include anouter band 675 that surrounds the distal tip 685, thereby increasing thestrength and rigidity of the distal tip. As mentioned above, the presentdisclosure, particularly the embodiment included in FIG. 6A, cocontemplates directing the laser-induced pressure wave and/or cavitationevent toward the guidewire lumen 680 and/or the guidewire 690 such thatthe pressure waves excite and vibrate the guidewire 690. A means fordirecting the laser-induced pressure wave and/or cavitation eventtowards the guidewire lumen 680 or the guidewire 690 within theguidewire lumen includes disposing the emitter(s) 620 proximate thedistal end 690 of the catheter 600 and/or proximate the distal end ofthe outer band 675 such that the emitter(s) 620 is recessed from thedistal tip 685 of the catheter 600 and/or proximate the distal end ofthe outer band 675 along the longitudinal axis of the catheter. Byrecessing the emitter(s) 620 from the distal tip 685 of the catheter 600and/or proximate the distal end of the outer band 675, the laser-inducedpressure wave and/or cavitation event may be directed toward theguidewire lumen 680 and/or the guidewire 690.

An additional means for directing the laser-induced pressure wave and/orcavitation event towards the guidewire lumen 680 or the guidewire 690within the guidewire lumen includes directing the emitter(s) 620 towardthe guidewire lumen 680 or the guidewire 690. For example, as discussedabove, the terms “emitter” as used herein may refer to an end portion ofa fiber or an optical component that emits light from a distal endthereof. The emitter 620 is directed towards the guidewire lumen 680and/or the guidewire 690 because the optical fiber is tapered in amanner that the light emitted therefrom is directed radially inwardtowards the guidewire lumen 680 and/or the guidewire 690. As illustratedin FIG. 6A, the guidewire lumen 680 and/or guidewire 690 may extendlongitudinally distal of the emitter 620. Accordingly, as the laserlight is emitted from the emitter(s) 620, the light interacts with theliquid medium, and the liquid medium absorbs the light energy, therebycreating vapor bubbles and cavitation events therein and/or producingresultant laser-induced pressure waves that cause the guidewire lumen680 and/or guidewire 690 to excite and/or vibrate.

Referring to FIG. 6A′, there is depicted an alternate embodiment of thepresent disclosure, particularly an alternate embodiment of a means fordirecting the laser-induced pressure wave and/or cavitation eventtowards the guidewire lumen 680 or the guidewire 690. Similar to theembodiment discussed above with respect to FIG. 6A, the embodiment inFIG. 6A′ includes a catheter 600′ having a plurality emitters 615, aninflation lumen 610, one or more liquid medium ports 670, and aguidewire lumen 680, and an outer band 675 that surrounds the distal tip685. This embodiment also includes a cap 695 having a guidewire lumen698 extending therethrough.

The cap 695 can be either removably coupled to the catheter 600′,particularly removably coupled to the outer band 675, or the cap can bepermanently affixed to the catheter 600′, particularly permanentlyaffixed to the outer band 675. The cap 695 includes a proximal (forexample, interior) side 694 and a distal (for example, exterior) side.The interior side 694 can be tapered such that a cavity 692 formsbetween the distal end of the catheter 600′ and the interior side 694 ofthe cap 695, thereby allowing the liquid medium to enter and collectwithin the cavity 692 after exiting the inflation lumen 610′. AlthoughFIG. 6A′ is depicted as having a catheter 600′ with a flush distal endand a tapered, recessed cap 695 to create a cavity between the catheter600′ and the cap for the liquid medium to collect, the presentdisclosure also contemplates having catheter with a recessed distal end,as depicted in FIG. 6A, that could be used in conjunction with a caphaving a flush or recessed interior side to create a cavity for theliquid medium to collect. Accordingly, as the laser light is emittedfrom the emitter(s) 620, the light interacts with the liquid mediumwithin the cavity 692, and the liquid medium absorbs the light energy,thereby creating vapor bubbles and cavitation events therein and/orproducing resultant laser-induced pressure waves that can cause theguidewire lumen 680 and/or guidewire 690 to excite and/or vibrate.

Referring to FIG. 7, there is depicted an alternate embodiment of thecatheter 700 of the present disclosure, particularly an alternateembodiment of a means for directing the laser-induced pressure waveand/or cavitation event towards the guidewire lumen 710 or the guidewire(not shown). As discussed above, the laser light is emitted from theemitter(s), the light interacts with the liquid medium (introduced intothe balloon catheter 750 through ports 770), and the liquid mediumabsorbs the light energy, thereby creating vapor bubbles and cavitationevents therein and/or producing resultant laser-induced pressure waveswithin the balloon catheter 750. This embodiment comprises the inclusionof pressure-wave reflective material in the balloon 750 such that uponthe pressure waves reaching the pressure-wave reflective material in theballoon, the reflective material re-directs at least a portion of thelaser-induced pressure wave toward the guidewire lumen 710 and/orguidewire (not shown) to excite and/or vibrate.

The pressure-wave reflective material may include a polymer having ahigher or harder durometer in comparison to the materials traditionallyused in balloons, such as polyethylene, polyurethane, andpolytetrafluoroethylene. The increased durometer and hardness of thepressure-wave reflective material may be achieved by including a fillerwithin the polymer matrix of a single layered balloon, increasing thecross-linking between polymer within the single layered balloon,selecting a harder polymer (in comparison to the traditional balloonmaterials), or co-extruding an additional harder polymer layer with thetraditional polymer layer. If a co-extruded construction is used tomanufacture the balloon, then the harder layer may be included on eitherthe interior or exterior of the balloon, and the traditional layerhaving the lower hardness will be on the opposite side of the balloon.Additionally, a three layered co-extruded structure may be used tomanufacture the balloon such that the harder layer is sandwiched betweentwo traditional lower durometer layers.

Referring to FIG. 8, there is depicted another alternate embodiment ofthe catheter 800 of the present disclosure, particularly an alternateembodiment of the catheter that comprises a pressure-wave reflectiveelement 880 over the balloon 850. The pressure-wave reflective element880 has multiple purposes, namely (1) the pressure-wave reflectiveelement 880 reduces or prevents the formation of vapor bubbles exteriorof the pressure-wave reflective element 880 and/or the balloon 850, (2)upon the pressure waves reaching the pressure-wave reflective element880, the reflective element 880 re-directs at least a portion of thepressure waves toward the guidewire lumen 810 and/or guidewire (notshown) to excite and/or vibrate the guidewire, and (3) the pressure-wavereflective element 880 reinforces the balloon 850, Accordingly, thepressure-wave reflective element 880 is (1) a means for reducing orpreventing the formation of cavitation bubbles exterior of thepressure-wave reflective element 880 and/or the balloon 850, (2) a meansfor re-directing at least a portion of the pressure waves toward theguidewire lumen 810 and/or guidewire to excite and/or vibrate theguidewire, and/or (3) a means for reinforcing the balloon 850.

Although the pressure-wave reflective element 880 is illustrated overthe balloon 850 in FIG. 8, the pressure-wave reflective element 880 maybe on the inside (interior) of the balloon 850, such as an inside layer,or the pressure-wave reflective element 880 may be incorporated orintegrated into the balloon 850 itself. Additionally, the pressure-wavereflective element 880 may cover a portion of the balloon 850, asdepicted in FIG. 8, or the pressure-wave reflective element 880 maycover the entire balloon 850. Regardless of whether the pressure-wavereflective element 880 is directly or indirectly coupled to the balloon850, the pressure-wave reflective element 880 is capable of expandingand contracting with the balloon 850. Accordingly, both thepressure-wave reflective element 880 and the balloon 850 have anexpanded state and a contracted state.

The pressure-wave reflective element 880 may be directly coupled to theworking portion 855 of the balloon 850 or indirectly coupled to theworking portion 855 of the balloon 850. The pressure-wave reflectiveelement 880 may be directly coupled to the working portion 855 of theballoon 850 by being affixed to the working portion 855 by a chemicalbond, mechanical fixation or some other means of affixation. Thepressure-wave reflective element 880 may be indirectly coupled to theworking portion 855 of the balloon 850 by directly coupling thepressure-wave reflective element 880 to the proximal end of the balloon850, the distal end of the balloon 850, the tapered ends of the balloon,and/or the catheter, including the structure that creates the guidewirelumen. Indirectly coupling the pressure-wave reflective element 880 tothe working portion 855 of the balloon 850 allows the pressure-wavereflective element 880 to expand and contract with the balloon 850 uponinflation and deflation, respectively, but it also allows thepressure-wave reflective element 880 to expand and contract in a mannersuch that the pressure-wave reflective element 880 is not permanentlyattached to the working portion 855 of the balloon 850. That is,indirectly coupling the pressure-wave reflective element 880 to theworking portion 855 of the balloon 850 allows the pressure-wavereflective element 880 to expand and contract separately from theballoon 850 but respectively with the balloon.

The pressure-wave reflective element 880 may be constructed of abiocompatible material, including either a polymeric material or ametallic material, such as nitinol, which is a nickel-titanium alloy.The pressure-wave reflective element 880 may be a solid structure or aporous scaffolding structure, as shown in FIG. 8. As discussed in moredetail below, the present disclosure contemplates that the pressure-wavereflective element 880 may comprise various shapes and configuration.For example, the sizes of the pores or openings within the scaffoldingstructure may be adjusted to control the amplitude or direction of thepressure waves approaching the target tissue.

Regarding the pressure-wave reflective element's ability to reduce orprevent the formation of vapor bubbles exterior of the pressure-wavereflective element 880 and/or the balloon 850, it may be preferable forthe pressure-wave reflective element 880 to be porous and thereby haveopenings 885. Referring to FIGS. 15A-15F, the openings 885 within thepressure-wave reflective element 880 may prevent the formation of largesized vapor bubbles on the exterior of the balloon 880. The openings 885not only allow the pressure waves to pass therethrough, but the quantityand size of the openings 885′, particularly with respect to theremainder of the structural mass 887 (or portions thereof) ofpressure-wave reflective element 880, may also limit the size of thevapor bubbles that can form on the exterior of the balloon 850. Therelationship between the open area and the closed area (or the ratio ofthe open area to the overall area) within the pressure-wave reflectiveelement 880 should be such that a sufficient amount of the pressurewaves pass through the pressure-wave reflective element 880. And thesize of the openings 885 should allow the pressure waves to passtherethrough, while also limiting the size of the vapor bubbles that canform on the exterior of the balloon 850. Accordingly, it may bedesirable for the percentage of the open area to the overall area of thepressure-wave reflective element 880 to be between 1 percent-99 percent,including any increment therebetween such as 2 percent, 3 percent, 4percent, 5 percent, 6 percent, 7 percent, 8 percent, 9 percent, 10percent, . . . , 15 percent . . . 20 percent, . . . , 25 percent, . . ., 30 percent, . . . , 35 percent, . . . , 40 percent, . . . , 45percent, . . . , 50 percent, . . . , 55 percent, . . . , 60 percent, . .. , 65 percent, . . . , 70 percent, . . . , 75 percent, . . . , 80percent, . . . , 85 percent, . . . , 90 percent, 91 percent, 92 percent,93 percent, 94 percent, 95 percent, 96 percent, 97 percent, and 98percent. It may also be desirable for the ratio of the open area to theoverall area of the pressure-wave reflective element 880 to be within aparticular range such as between 5 percent to 95 percent, 10 percent to90 percent, 15 percent to 85 percent, 20 percent to 80 percent, 25percent to 75 percent, 30 percent to 70 percent, 35 percent to 65percent, 40 percent to 60 percent, and 45 percent to 55 percent.Additionally, for any of the above listed ratios it may be desirable foreach opening 885 to have a particular size, such as between 10 micronsto 10,000 microns (1 millimeter), including any increment therebetweensuch as 10 microns, . . . , 12.5 microns, . . . , 15 microns, 17.5microns, . . . 20 microns, . . . 30 microns, . . . 40 microns, . . . 50microns, . . . 75 microns, . . . 100 microns, . . . 125 microns, . . . ,150 microns, . . . 175 microns, . . . , 200 microns, . . . 300 microns,. . . 400 microns, . . . , 500 microns, . . . , 600 microns, . . . , 700microns, . . . , 800 microns, . . . , 900 microns, . . . , 1000 microns,. . . , 2000 microns, . . . , 3000 microns, . . . , 4000 microns, . . ., 5000 microns, . . . , 6000 microns, . . . , 7000 microns, . . . , 8000microns, . . . , 9000 microns, . . . , 9100 microns, . . . , 9200microns, . . . , 9300 microns, . . . , 9400 microns, . . . , 9500microns, . . . , 9600 microns, . . . , 9700 microns, . . . , 9800microns, . . . , 9900 microns, . . . and 10,000 microns. It may also bedesirable for the size openings 850 within the pressure-wave reflectiveelement 880 to be within a particular range such as between 1000 to 9000microns, 2000 to 8000 microns, 3000 to 7000 microns, 4000 to 6000microns, and 4500 to 5500 microns.

The pressure-wave reflective element's ability to reduce or prevent theformation of vapor bubbles exterior of the pressure-wave reflectiveelement 880 and/or the balloon 850 potentially reduces the existenceand/or the size of the vapor bubbles formed on the exterior of theballoon catheter, which in turn reduces the likelihood that vaporbubbles will be created and expand and contract between the ballooncatheter and the vasculature wall. And reducing or preventing expansionand contraction of vapor bubbles between the balloon catheter and thevasculature wall prevent or reduce the likelihood that a hydraulic forceor pressure will be applied to the vascular occlusion and/or to thewalls of the vessel, thereby preventing and/or minimizing potentialdamage to the vasculature itself.

Regarding the pressure-wave reflective element's ability to reinforcethe balloon, the pressure-wave reflective element may reduce or preventthe balloon's ability, particularly the balloon's working length'sability, to expand and contract upon creation of the vapor bubblestherein. Reducing the balloon's ability, particularly the balloon'sworking length's ability, to expand and contract upon the formation ofvapor bubbles within the balloon, reduce or prevent the balloon 850 fromapplying a hydraulic force or pressure to the vascular occlusion and/orto the walls of the vessel.

The openings 850′ in the pressure-wave reflective element 880′ depictedin FIG. 15A are shown as squares, the openings 850″ (and 850″″) in thepressure-wave reflective element 880″ (and pressure-wave reflectiveelement 880″″) depicted in FIG. 15B (and FIG. 15E) are shown asdiamonds, the openings 850″″″ in the pressure-wave reflective element880″″″ are shown as hexagons, which are disposed around thecircumference of pressure-wave reflective element, as well as along itslength. Although the openings in the pressure-wave reflective element inthese figures are illustrated as squares, diamonds and hexagons, theopenings may have an alternate shape, such as a circle, oval, triangle,rectangle, polygon, pentagon, heptagon, octagon, nonagon, and decagon.For example, FIG. 15C is a side view of a pressure-wave reflectiveelement 880″ comprising a plurality of openings formed by a helicalstructure wound in a particular direction (for example, clockwise orleft to right), and FIG. 15D is a side view of a pressure-wavereflective element 850′″ comprising a plurality of openings formed by ahelical structure wound in an alternate direction (for example,counter-clockwise or right to left). Additionally, the two helicallyformed pressure-wave reflective elements may be combined to form thepressure-wave reflective element 880′″″ depicted in FIG. 15E. Thepressure-wave reflective element 880′″″ depicted in FIG. 15E is similarto the pressure-wave reflective element 880″ depicted in FIG. 15B, butthe pressure-wave reflective element 880″ depicted in FIG. 15B isbraided and the pressure-wave reflective element 880′″″ depicted in FIG.15E is wound or formed by one or two hypotubes. Additionally, thestructural mass 887′″″ (or portions thereof) of the pressure-wavereflective element 880′″″ depicted in FIG. 15E is larger than thestructural mass (or portions thereof 1128″) of the pressure-wavereflective element 880″ depicted in FIG. 15B because braided materialsare generally smaller in size. Referring to FIG. 15F, the structuralmass 887″″″ (or portions thereof) of the pressure-wave reflectiveelement 880″″″, are substantial in comparison to the size of thehexagonal openings 885″″″. It may be desirable for the ratio of the areaof the openings 885 to the area of the structural mass 887 of thepressure-wave reflective element 880 to be between 1:0.01 and 1:100,including any increment therebetween such as 1:0.01, 1:0.02, 1:0.03,1:0.04, 1:0.05, 1:0.06, 1:0.06, 1:0.07, 1:0.08, 1:0.09, 1:0.10, . . . ,1:0.20, . . . , 1:0.30, . . . , 1:0.40, . . . , 1:0.50, . . . , 1:0.60,. . . , 1:0.70, . . . , 1:0.80, . . . , 1:0.90, 1:0.91, 1:0.92, 1:0.93,1:0.94, 1:0.95, 1:0.96, 1:0.97, 1:0.98, 1:0.99, 1:1, 1:2, 1:3, 1:4, 1:5,1:6, 1:7, 1:8, 1:9, 1:10, . . . , 1:15, . . . 1:20, . . . , 1:25, . . ., 1:30, . . . , 1:35, . . . , 1:40, . . . , 1:45, . . . , 1:50, . . . ,1:55, . . . , 1:60, . . . , 1:65, . . . , 1:70, . . . , 1:75, . . . ,1:80, . . . , 1:85, . . . , 1:90, 1:91, 1:92, 1:93, 1:94, 1:95, 1:96,1:97, 1:98, 1:99, and 1:100. It may also be the ratio of the area of theopenings 885 to the area of the structural mass 887 of the pressure-wavereflective element 880 to be within a particular range such as between1:0.01 and 1:100, 1:0.10 and 1:90, 1:0.20 and 1:80, 1:0.30 and 1:70,1:0.40 and 1:60, 1:0.50 and 1:50, 1:0.60 and 1:40, 1:0.70 and 1:30;1:0.80 and 1:20, 1:0.90 and 1:10, 1:0.90 and 1:9, 1:0.90 and 1:8, 1:0.90and 1:7, 1:0.90 and 1:6, 1:0.90 and 1:5, 1:0.90 and 1:4, 1:0.90 and 1:3,1:0.90 and 1:2, or any increments therebetween, such as 1:0.91 and1:1.9, 1:0.92 and 1:1.8, 1:0.93 and 1:1.7, 1:0.94 and 1:1.6, 1:0.95 and1:1.5, 1:0.96 and 1:1.4, 1:0.97 and 1:1.3, 1:0.98 and 1:1.2 and 1:0.99and 1:1.01.

In some embodiments, the devices and methods of the present disclosurecan also be used to deliver laser-induced pressure waves to disrupt avascular occlusion or restriction and/or deliver a therapeutic agentusing a substantially solid light absorbing material instead of liquidmedium. In some circumstances, pairing a laser that emits a specificwavelength of light with a light absorbing material designed to absorblight at that wavelength can significantly increase the energyefficiency of the resultant laser-induced pressure waves produced by thereaction. The use of such pairings can ultimately reduce the energyinput required to treat a vascular occlusion or restriction and/ordeliver a therapeutic agent, which can increase the safety of theprocedure and reduce costs. For example, the balloon assembliesdescribed in the present disclosure can be filled with air or asubstantially inert liquid medium (for example, saline) instead ofcontrast medium, which can significantly reduce the amount and size ofvapor bubbles produced along with the laser-induced pressure waves.Because the laser-induced pressure waves can propagate outside of theballoon to disrupt a vascular occlusion and/or deliver a therapeuticagent, it can be advantageous in some circumstances to reduce (forexample, by filing the balloon catheter with saline) or eliminate (forexample, by filling the balloon catheter with air or inert gas) theproduction of vapor bubbles. In other cases, liquid medium used toinflate the balloon can be pre-treated to remove the amount of gasdissolved in it using methods known to one of ordinary skill in the artbased on the present disclosure, as this can also reduce the amount ofvapor bubbles generated along with the laser-induced pressure waves.

For certain applications, it may be desirable to increase the amountand/or the size of vapor bubbles produced along with a laser-inducedpressure wave that is generated by emitting laser light energy into acorresponding light absorbing liquid medium. For example, when enteringsmaller diameter sized blood vessels, the size of the catheter may belimited. In some cases, the force that vapor bubbles exert on tissue(for example, a vascular occlusion) may be proportional to the size ofthe individual vapor bubbles created, as the bubbles expand and contractafter laser light energy is emitted into liquid medium and alaser-induced pressure wave is generated. That is, the strength of thelaser-induced pressure wave and/or the size of the vapor bubble may belimited with the use of a non-gas saturated liquid medium. One manner bywhich the size of individual vapor bubbles can be increased (forexample, to impart greater amount of force on a particular tissue) is tosaturate the liquid medium with gaseous substances so that the gaswithin the liquid medium exhibits a higher vapor pressure as compared tothat of the liquid medium without such gas. Suitable gaseous substancesthat may be used to create gas-saturated liquid medium include, but arenot limited to, ambient air, carbon dioxide, iodine gas, oxygen,nitrogen, compressed air, nitrous oxide, and combinations of these.

The higher vapor pressure of the gaseous substance added to the liquidmedium will cause the gaseous substance to return to a gaseous statefaster (under smaller pressure fluctuations) than the liquid medium. Inother words, less pressure is required to cause the saturated gaseoussubstances to come out of solution, resulting in the creation of largervapor bubbles, and concomitantly, a greater amount of force. In somecases, the use of gas-saturated liquid medium allows for the use oflaser light energy at decreased intensities, or decreased pulses orpulse durations, without any accompanying decrease in the overall forcegenerated by the vapor bubbles (as each vapor bubble is larger). Thiscan enhance both the safety and efficacy of the procedure beingperformed.

The gaseous substances can be imparted to the liquid medium throughvarious means, including under pressure, through mechanical agitation,and/or by bubbling the gas into the liquid medium. In some cases,gas-saturated liquid medium can be prepared prior to a procedure andthen injected into a balloon prior to performing the procedure.Additionally or alternatively, gaseous substances can be delivered intothat liquid medium that is already present in the catheter balloon.

The gases and/or gaseous substances may be dissolved and quantified bythe amount of gases present in a 1 kg of the liquid medium. The maximumamount of gas that will dissolve in the liquid medium is dependent onthe solubility of the particular gas in that liquid medium, thepressure, and the temperature as described by Henry's law of gassolubility. For example, carbon dioxide may be dissolved into water at aconcentration of 1.25 g/kg of water or less at 30 degrees Celsius underatmospheric pressure. And upon dissolving carbon dioxide into water orsaline, an overall concentration between 0.25-3.5 g/kgH₂O is produced.The concentrations of other dissolved gases in a kilogram of liquidmedium ranges from 1 mg-1 g/kg for iodine, 5-80 mg/kg for oxygen, 5-40mg/kg for nitrogen, 5-500 mg/kg for room air, and 0.1-4 g/kg for nitrousoxide.

The gases and/or gaseous substances may be dissolved in quantities abovethe theoretical limit, which is known as super saturation. Thetheoretical limit is described by Henry's law as mentioned previously.By dissolving the gases under increased pressure or decreasedtemperature and then returning it to normal atmospheric conditions, itis possible to dissolve a larger quantity of gas then is possible atatmospheric conditions. For example, 2.5 g of carbon dioxide may bedissolved into 30 degrees Celsius water under 2 atm of pressure, andthen returned to atmospheric pressure. For any dissolved gas, thesaturation percentage is defined by the concentration of gas over thetheoretical maximum concentration. For any of the previously mentionedgases in a supersaturated solution, the saturation percentage can rangefrom 100-300 percent.

The use of a gas saturated liquid medium or super saturated liquidmedium may also increase the laser-induced pressure wave caused by theinteraction of the laser light and the liquid medium. That is, the gassaturated liquid medium or super saturated liquid medium may containlarger potential energy, which when activated by the laser light, maycreate a larger laser-induced pressure wave in comparison to alaser-induced pressure wave created by the interaction of laser lightand a non-gas saturated liquid medium.

Suitable light absorbing material can be any agent capable of absorbinglight energy and producing a laser-induced pressure wave. For example,the light absorbing material can contain an aromatic hydrocarbon withiodine bonded to it, such as iodinated x-ray contrasts. Low osmolar,non-ionic, iodinated, and radio-opaque contrasts are also suitable lightabsorbing materials that can be used to produce laser-induced pressurewaves. Other light absorbing materials include, but are not limited to,iodinated contrasts such as Diatrizoic acid, Metrizoic acid, lodamide,lotalamic acid, loxitalamic acid, loglicic acid, Acetrizoic acid,locarmic acid, Methiodal, Diodone, Metrizamide, lohexol, loxaglic acid,lopamidol, lopromide, lotrolan, loversol, lopentol, lodixanol, lomeprol,lobitridol, loxilan, lodoxamic acid, lotroxic acid, loglycamic acid,Adipiodone, lobenzamic acid, lopanoic acid, locetamic acid, Sodiumiopodate, Tyropanoic acid, Calcium iopodate, lopydol, Propyliodone,lofendylate, Lipiodol, non-iodinated contrasts such as Barium sulfate,MRI contrast agents such as Gadobenic acid, Gadobutrol, Gadodiamide,Gadofosveset, Gadolinium, Gadopentetic acid, Gadoteric acid,Gadoteridol, Gadoversetamide, Gadoxetic acid, Ferric ammonium citrate,Mangafodipir, Ferumoxsil, and Ferristene Iron oxide nanoparticles,Perflubron, Glucose and other carbohydrates, Albumen and other proteins,Nitroglycerin or other vasodilators, Hydrocarbons such as Oils,Alcohols, or other organic functional groups (Amines, Alkanes, Carboxyl,and the like), blood/tissue products such as Platelet Rich Plasma (PRP),packed red cells, plasma, platelet, fat, Charcoal, biocompatiblematerials such as stainless steel, biopolymers, and bioceramics, orother pharmacological agents which contain a combination of aromaticcarbon rings and functional groups such as Salicylic acid,Acetylsalicylic acid, Methyl salicylate, Mesalazine, Aspirin,Acetaminophen, Ibuprofen, Clopidogrel, or other pharmacological and/orbiological agents which may be compatible with the medical proceduresdescribed herein.

Suitable light absorbing material can also include those materialscapable of absorbing wavelengths in the UV spectrum. For example, lightabsorbing materials can include, but are not limited to, PABA, Padimate0, Phenylbenzimidazole sulfonic acid, Cinoxate, Dioxybenzone,Oxybenzone, Homosalate, Menthyl anthranilate, Octocrylene, Octylmethoxycinnamate, Octyl salicylate, Sulisobenzone, Trolamine salicylate,Avobenzone, Ecamsule, 4-Methylbenzylidene camphor, Tinosorb M, TinosorbS, Tinosorb A2B, Neo Heliopan AP, Mexoryl XL, Benzophenone-9, Uvinul T150, Uvinul A Plus, Uvasorb HEB, Parsol SLX, or Amiloxate, Silicon andits various atomic structures, Cadmium telluride, Copper indium galliumselenide, Gallium arsenide, Ruthenium metalorganic dye, Polyphenylenevinylene, Copper phthaloncyanine, Carbon fullerenes and derivatives,Carbon compounds such as Graphite, Graphene, Diamond, Charcoal,Titianium and oxides, Nickel and oxides, Gold, Silver, Zinc and oxides,Tin and oxides, Aluminum and oxides, or alloys or ceramics of thepreceding metals.

Light absorbing material may be combined with various other compounds tofacilitate their attachment to a substrate. For example, light absorbingmaterials may be combined with various compounds (for example,solubilizing agents) that aid in the generation of a solution or mixturecomprising the light absorbing material, which can be used to coat thesubstrate. In some embodiments, a biodegradable and biocompatiblehydrophobic polymer may be used as a light absorbing material. Forexample, the biodegradable and biocompatible hydrophobic polymer may bepoly(glycerol sebacate acrylate) (PGSA), or variations and combinationsthereof, which can be crosslinked using ultraviolet light. Ultravioletlight may be emitted from the distal end of a catheter, which may bedisposed within or outside of an inflatable balloon, to activate thePGSA, for example.

Other light absorbing material can also include agents havingadhesive-like properties, and in some cases, the light absorbingproperties of these agents can be in addition to, or independent of,their use as adhesives. For example, light absorbing materials caninclude, but are not limited to, cyanoacrylates, bovine serum albumin(BSA)-glutaraldehyde, fibrin sealants, gelatin matrix thrombin, gelatinsponge, oxidized cellulose, collagen sponge, collagen fleece,recombinant factor VIIa, and the like. In some embodiments, the lightabsorbing material may comprise hydrophobic functional groups, such ashexanoyl (Hx; C6), palmitoyl (Pam; C16), stearoyl (Ste; C18), and oleoyl(Ole; C18 unsaturated) groups, so as to resist being washed out ordisengaged from their substrate in predominately aqueous environments(for example, vascular tissue). Such light absorbing materials caninclude, but are not limited to, 10Ole-disuccinimidyl tartrate,10Ste-disuccinimidyl, and variations and combinations thereof.

Light absorbing material can be configured to exhibit high absorption oflight energy from an emitter. Light energy can be emitted at anysuitable wavelength capable of generating laser-induced pressure waves.Light energy can be emitted between about 1 nanometer and about 1millimeter. In some cases, light can be emitted from about 10 nanometersto about 5000 nanometers. In some cases, light can be emitted from about100 nanometers to about 1000 nanometers. In some cases, light can beemitted from about 250 nanometers to about 750 nanometers. In somecases, light can be emitted from about 300 nanometers to about 600nanometers. In still other cases, light can be emitted from about 300nanometers to about 350 nanometers.

In general, the light absorbing material can be located anywhere withinthe balloon catheter, so long as it generally intersects with the pathof light emitted from the emitter, thereby generating a reaction betweenthe light and the absorbing material. In some embodiments, the lightabsorbing material may be substantially solid (for example, stable in agenerally solid state, such as metals and metal alloys). Substantiallysolid light absorbing material can be used to construct various portionsof the components of the catheter that are located within the balloon,and/or substantially solid light absorbing material can be used toconstruct a separate structure that is independent of another cathetercomponent.

In some embodiments, the light absorbing material can be applied to aseparate supporting structure (such as, a support structure that is notpredominately made of light absorbing material, or a support structurethat is not being used as a light absorbing material) and used togenerate laser-induced pressure waves using the devices and methods ofthe present disclosure. In some embodiments, the light absorbingmaterials are stable only in liquid, gel, or semi-liquid forms. In theseembodiments, the light absorbing material can be included as part of aformulation or coating that is suitable for application to a supportstructure, such as impregnated in hydrogel or other solid supportmatrix. In some embodiments, the light absorbing materials can be partof a formulation or coating containing other agents that facilitatetheir placement on and/or adherence to a support structure. For example,solid absorbing materials can be formulated with coating agents,thickening agents, adhesive agents, and/or other pharmaceutical orbiological agents that are suitable for use with the devices and methodsof the present disclosure.

Referring to FIGS. 12 and 12A, the distal end of catheter 1200 of thepresent disclosure can include one or more layers of emitters arrangedcircumferentially around or adjacent to an inner lumen 110, as well as asupport structure for use as a substrate for the application of lightabsorbing material. For example, FIG. 12A is a cross-sectional viewalong the plane demarcated by line A-A in FIG. 12, and the lightabsorbing material support structure 174 is shown exiting the innerlumen 110 through port 172. The light absorbing material can be appliedas a coating, as described above, on the distal end of the supportstructure 174 exposed to the inner cavity of the balloon 150, and thedistal end support structure 174 can be positioned such that itgenerally intersects with the path of the light emitted from the distalend of the emitters 115, thereby generating a reaction between the lightand the absorbing material. The balloon 150 can be inflated with aninert gas or liquid, as described above, through one or more inflationmedium ports. Additionally, the distal end of the light absorbingmaterial support structure 174 can be extended to intersect generallywith the path of light emitted from any of the emitters that aredepicted in FIGS. 3A-3C. The distal end of the light absorbing materialsupport structure 174 can also exit any ports 172 located along theinner lumen, as shown in FIG. 12.

In some embodiments, as shown in FIG. 12A, the light absorbing materialcan be applied to various surfaces within the balloon 150 itself insteadof being applied to a support structure. For example, the lightabsorbing material can be applied as a coating to the inner surface ofthe balloon 152 or portions thereof. The laser light emitted from thedistal end of the emitters 115 can be directed upward and/or outwardsuch that it can react with the light absorbing material 150 to generatea laser-induced pressure wave, without the need for an additionalsupport structure. Additionally, the light absorbing material can beapplied as a coating to the external surface of the inner lumen 112. Inthis case, the laser light emitted from the distal end of the emitters115 can be directed downward and/or inward such that it can react withthe light absorbing material 112 to generate a laser-induced pressurewave, without the need for an additional support structure. In otherembodiments, the light absorbing material can also be applied as acoating to one or more proximal surfaces 1031 of the distal tip of thecatheter 1030, as shown in FIG. 13. In this case, laser light emittedfrom the distal portion 1025 of the laser catheter 1020 within theballoon catheter 1050 can contact the light absorbing material locatedon a proximal surface 1031 of the distal tip 1030 to generate alaser-induced pressure wave, without the need for an additional supportstructure.

Referring to the flow chart in FIG. 14, the present disclosure includesa method for treating a subject with a vascular obstruction orrestriction 1400 using embodiments of the catheter described herein.Although it is not illustrated in FIG. 14, it may be desirable to use alaser catheter to ablate at least a portion of the vascular occlusion inthe vessel of the subject prior to performing the method set forth inFIG. 14 and/or using the a laser catheter to ablate at least a portionof the vascular occlusion in the vessel prior to and/or subsequent toperforming any of the steps set forth in FIG. 5. The method 1400 in FIG.14 includes locating a vascular obstruction or restriction in the vesselof a subject 1410. The next step, which is optional, includes locating aguidewire at the occlusion and/or inserting a guidewire through theocclusion 1415. Thereafter, any of the embodiments of the cathetersdescribed herein may be slid over the guidewire and into the vasculaturesuch that the balloon catheter, which is coupled to the catheter, ispositioned adjacent to the vascular obstruction or restriction 1420. Asdiscussed herein, the emitters within the balloon catheter may be fixedor slidable with respect to the balloon catheter. For example, if theemitters are included with the laser catheter, which is slidable withinthe catheter and balloon of the balloon catheter, the emitters may bepositioned (and subsequently re-positioned) anywhere along the length ofthe balloon at a desired location. Additionally or alternatively, themethod 1400 includes inflating the balloon by delivering inflationmedium (for example, liquid medium comprising saline or gas mediumcomprising inert air) from the inner lumen of the catheter through oneor more inflation medium ports and into the balloon 1440. In some cases,if a light absorbing material support structure is being used, themethod 1400 includes optionally inserting and positioning the lightabsorbing material support structure into the balloon catheter such thatit lies in the general path of the laser light emitted from the catheter1445. In other cases, the light absorbing material is applied as acoating to one or more surfaces within the balloon catheter, and step1445 is not performed. Instead, the method 1400 includes activating atleast one energy source coupled to at least one emitter enclosed withinthe balloon catheter to send pulses of laser light energy to the areawhere the light absorbing material is located to produce propagatinglaser-induced pressure waves and disrupt a portion of the vascularocclusion 1450. In some cases, the method 1400 includes activating atleast one energy source coupled to at least one emitter enclosed withinthe balloon catheter to send pulses of laser light energy to the areawhere the light absorbing material is located to produce propagatinglaser-induced pressure waves to deliver a therapeutic agent to thevascular obstruction or restriction and/or the vascular tissue near theobstruction or restriction 1460. Delivering light energy through aproximal emitter to disrupt a portion of a vascular obstruction orrestriction and/or to deliver a therapeutic agent can be performed inany sequence, if at all, as part of the method 1400. For example, step1450 could be performed without performing step 1460, step 1460 could beperformed without performing step 1450, step 1450 could be performedserially while performing step 1460, such that step 1450 is performedfirstly and step 1460 is performed secondly, step 1450 could beperformed serially while performing step 1460, such that step 1460 isperformed firstly and step 1450 is performed secondly, or steps 1450 and1460 could be performed in parallel. Upon completing step 1450 and/orstep 1460, the balloon catheter can optionally be repositioned withinthe vasculature and adjacent another portion thereof. Similarly, uponcompleting step 1450 and/or step 1460, the emitter(s) can optionally berepositioned within the balloon catheter, such as by sliding theemitters (or a laser catheter) within the balloon catheter (and catheterholding the balloon catheter). Either or both the balloon can berepositioned within the vasculature or the emitter(s) within the ballooncatheter can be repositioned. The method 1400 also includes ending theprocedure when the desired therapeutic outcome is obtained, or repeatingany of 1410 through 1460 as may be necessary to treat a subject having avascular obstruction or restriction. Furthermore, if step 1460 is notperformed in the method depicted in FIG. 14, a drug eluting (coated)balloon (DEB or DCB) catheter may be used to deliver drugs to theremnants of the vascular occlusion. Disrupting the vascular occlusionwith the laser-induced pressure waves prior to utilizing a DEB mayincrease the effectiveness of the drugs being applied to the vascularocclusion because to the laser-induced pressure waves disrupt theintraluminal as well as medial (within the tissue layer of the vascularwall) vascular obstruction or restrictions (for example, calciumdeposits), thereby creating a pathway for the drug to enter theintraluminal and medial portions of the vasculature and/or vascularocclusion.

Although the method illustrated in FIG. 14 depicts step 1420, whichincludes positioning the balloon catheter adjacent the vascularocclusion or restriction, being performed prior to step 1425, whichincludes positioning the emitters within the balloon at a desiredlocation, step 1425 may be performed after or in parallel with step1420. Additionally, although the method illustrated in FIG. 14 depictsstep 1420 and step 1425 as occurring prior to step 1440, which includesinflating the balloon catheter with liquid medium, step 1440 may beperformed prior to or in parallel with one or both of step 1420 or step1425. Additionally, although the method illustrated in FIG. 14 depictsstep 1420 and step 1425 and 1440 as occurring prior to step 1445, whichincludes inserting light absorbing material support structure into theballoon catheter in the general path of the laser light to be emitted,step 1445 may be performed prior to or in parallel with one or both ofstep 1420 or step 1425. That is, steps 1420, 1425, 1440 and 1445 may beperformed in any order.

Referring to FIGS. 16A and 16B, a laser catheter system 1610 generallyincludes a laser catheter 1612, a guidewire 1614, a catheter 1616, and ahandle 1618 that translatably couples the laser catheter 1612 to acatheter 1616 of a balloon catheter. The laser catheter 1612, theguidewire 1614, and the balloon catheter, including the catheter 1616thereof, may be similar to, for example, the components of the two-piececatheter systems or kits described herein. As a specific example, thelaser catheter 1612, the guidewire 1614, and the catheter 1616 may besimilar to the components described above in connection with FIGS.4A-4C, FIG. 10A and/or FIG. 13. The laser catheter 1612 is disposedwithin a lumen of the catheter 1616 and the handle 1618, and the lasercatheter 1612 includes a proximal coupling 1620 for coupling to thehandle 1618. The guidewire 1614 is disposed within a lumen of the lasercatheter 1612. The catheter 1616 includes a proximal coupling 1622 forcoupling to the handle 1618. The catheter 1616 also includes a balloonsurrounding a portion of the catheter 1616, and the distal end of thecatheter 1616 has an opening such that the laser catheter 1612 entersinto the balloon. For example, referring to FIG. 13, item 1010 is acatheter, and item 1020 is a laser catheter, and the laser catheter 1020slides through the catheter 1010 and into the opening of the balloon1050.

A liquid medium is introduced into the catheter 1616 distal to the lasercatheter 1612 within the balloon, particularly distal to the emitters ofthe laser catheter 1612 such that when the laser is activated, theliquid absorbs the light and creates laser-induced pressure waves and/orvapor bubbles and/or a cavitation event and resultant pressure waveswithin the balloon. The liquid is introduced via the lumen or a spacebetween the laser catheter 1612 and the catheter 1616, which in turnreceives the liquid from a proximal port 1624 coupled to the catheter1616.

Referring now to FIGS. 16A, 16B, 17A-16G, the handle 1618 generallyincludes a base 1626 that couples to the catheter 1616 and a drivemechanism 1628 that couples to the laser catheter 1612. As described infurther detail below, a portion of the drive mechanism 1628 istranslatably coupled to the base 1626 to facilitate translating thelaser catheter 1612 within the lumen of the catheter 1616 and within theballoon (for example, to the various positions shown in FIGS. 4A-4C).The drive mechanism 1628 may be translated to a proximal positionrelative to the base 1626 (see FIGS. 17A-17C), a distal positionrelative to the base 1626 (see FIGS. 17E and 17F), and an infinitenumber of intermediate positions therebetween (see FIGS. 17D and 17G).As a result, the laser catheter 1612 may be translated to correspondingpositions relative to the catheter 1616 and relative to the balloon.

Referring now to FIGS. 16A-19, the base 1626 includes an elongated,hollow frame 1630 that movably couples to the drive mechanism 1628. Theframe 1630 includes a proximal portion 1632, an intermediate portion1634, and a distal portion 1636. The proximal portion 1632 defines aproximal passageway 1638 for translatably receiving a shaft 1640 of thedrive mechanism 1628 therein. Referring specifically to FIGS. 18B, 18C,and 19, the proximal passageway 1638 may include a first key featurethat, by coupling to a second key feature of the shaft 1640, inhibitsrotation of the shaft 1640 relative to the frame 1630. For example, thesecond key feature of the shaft 1640 may be a non-circularcross-sectional area, and the first key feature of the proximalpassageway 1638 may be a cross-sectional area that is approximatelyidentical (that is, permitting sufficient clearance to permit relativelongitudinal translation, but inhibit relative rotation and transversetranslation) to the cross-sectional area of the shaft 1640, or across-sectional area that is approximately identical to a portion of thecross-sectional area of the shaft 1640. As a more specific example andas shown in FIGS. 18B, 18C, and 19, the shaft 1640 includesrectangle-like cross-sectional shape, with two opposing flat sidesurfaces 1642 and two opposing arcuate side surfaces 1644. The proximalpassageway 1638 includes a cross-sectional area that is approximatelyidentical to a portion of the cross-sectional area of the shaft 1640.Specifically, the proximal passageway 1638 is defined by four opposingflat side surfaces 1646 and two opposing arcuate side surfaces 1648. Theflat side surfaces 1646 and the arcuate side surfaces 1648 engage theflat side surfaces 1642 and the arcuate side surfaces 1644 of the shaft1640, respectively, to permit relative longitudinal translation, butinhibit relative rotation and transverse translation of the shaft 1640relative to the frame 1460. In the present example, the proximalpassageway 1438 is also defined by two additional opposing arcuate sidesurfaces 1649 that extend between the flat side surfaces 1646. Thearcuate side surfaces 1649 are disposed apart from the shaft 1640 toreduce sliding friction between the shaft 1640 and the frame 1630.

Referring specifically to FIGS. 18A, 18D, and 18E, the intermediateportion 1634 of the frame 1630 includes a first bearing portion 1650, asecond bearing portion 1652, and an opening 1654 extending therebetweenand aligned with the proximal passageway 1638. Each of the first andsecond bearing portions 1650, 1652 includes first and second bearingsurfaces 1656, 1658. The first and second bearing surfaces 1656, 1658rotatably support a control element 1660 of the drive mechanism 1628.Each of the first and second bearing portions 1650, 1652 also includes aclearance surface 1662 between the bearing surfaces 1656, 1658. Theclearance surface 1662 is also disposed radially inwardly relative tothe bearing surfaces 1656, 1658. The clearance surface 1662, togetherwith the opening 1654, facilitates driving engagement of the controlelement 1660 with the shaft 1640, as described in further detail below.Within the opening 1654, each of the first and second bearing portions1650, 1652 includes a guide surface 1664. The guide surface 1664 istranslatably coupled to the shaft 1640 and inhibits the shaft 1640 fromrotating within the frame 1630.

Referring briefly to FIGS. 17H-17J, to facilitate assembly of the base1626, each clearance surface 1662 may be monolithically coupled with thefirst bearing surface 1656, 1658. After positioning the shaft 1640within the frame 1630 and the control element 1660 over the firstbearing surface 1656, 1658 and the clearance surface 1662, eachclearance surface 1662 may couple to the second bearing surface 1656,1658 via, for example, press fit, one or more adhesives, snap connectors(not shown), or the like.

Referring to FIGS. 18A, 18F, and 18G, the distal portion 1636 of theframe 1630 may be similar to the proximal portion 1632 of the frame1630. That is, the distal portion 1636 defines a distal passageway 1666aligned with the opening 1654 for translatably receiving the shaft 1640.Referring specifically to FIGS. 18F, 18G, and 19 and in a similar mannerto the proximal passageway 1638, the distal passageway 1666 may includea first key feature that, by coupling to the second key feature of theshaft 1640, inhibits rotation of the shaft 1640 relative to the frame1630. For example, the second key feature of the shaft 1640 may be anon-circular cross-sectional area, and the first key feature of thedistal passageway 1666 may be a cross-sectional area that isapproximately identical to the cross-sectional area of the shaft 1640,or a cross-sectional area that is approximately identical to a portionof the cross-sectional area of the shaft 1640. In accordance with thespecific example described above and as shown in FIGS. 18F, 18G, and 19,the distal passageway 1666 includes a cross-sectional area that isapproximately identical to a portion of the cross-sectional area of theshaft 1640. Specifically, the distal passageway 1666 is defined by fouropposing flat side surfaces 1668 and two opposing arcuate side surfaces1670. The flat side surfaces 1668 and the arcuate side surfaces 1670engage the flat side surfaces 1642 and the arcuate side surfaces 1644 ofthe shaft 1640, respectively, to permit relative longitudinaltranslation, but inhibit relative rotation and transverse translation ofthe shaft 1640 relative to the frame 1630. In the present example, thedistal passageway 1666 is also defined by two additional opposingarcuate side surfaces 1672 that extend between the flat side surfaces1668. The arcuate side surfaces 1672 are disposed apart from the shaft1640 to reduce sliding friction between the shaft 1640 and the frame1630.

Referring again to FIGS. 16A-18G, at its proximal end, the frame 1630couples to a proximal cover 1676 (for example, via press fit, one ormore adhesives, or the like). The proximal cover 1676 includes aproximal aperture 1678 (see FIGS. 17F and 17G) for permitting the lasercatheter 1612 to extend into the frame 1630. At its distal end, theframe 1630 couples to a distal cover 1680 (for example, via press fit,one or more adhesives, or the like). The distal cover 1680 includes adistal aperture 1682 (see FIGS. 17F and 17G) for permitting the lasercatheter 1612 to extend out of the frame 1630 and into the catheter1616. The distal aperture 1682 press-fittingly receives a tube 1684 (forexample, a hypotube 1684) that extends into the shaft 1640 and receivesthe laser catheter 1612. The distal aperture 1682 also press-fittinglyreceives a distal coupling 1686 that detachably and sealingly couples tothe proximal coupling 1622 of the catheter 1616 of the balloon catheter.

Referring now to FIGS. 16A and 17A-17J, the drive mechanism 1628generally includes the shaft 1640 and the control element 1660.Referring specifically to FIGS. 17F-17J, the shaft 1640 includes a shaftpassageway 1688 for permitting the laser catheter 1612 to extend throughthe shaft 1640 and for receiving the tube 1684. The shaft 1640passageway 1688 press-fittingly receives a proximal coupling 1690 thatdetachably and sealingly couples to the proximal coupling 1620 of thelaser catheter 1612. As such, movement of the control element 1660relative to the base 1626 causes the shaft 1640 to translate within thebase 1626, and the laser catheter 1612 thereby translates within thelumen of the catheter 1616 and translates within the balloon.

The shaft 1640 passageway 1688 also receives a seal 1692, for example,an O-ring, which translatably engages the outer surface of the tube1684. As such, the seal 1692 inhibits the liquid in the shaft 1640passageway 1688 (received from the catheter 1616 via the distal coupling1686 and the hypotube 1684) from exiting the shaft 1640 by flowingbetween the shaft 1640 and the tube 1684.

As described briefly above, the control element 1660 is rotatablysupported by the frame 1630. The control element 1660 includes a firstengagement feature that couples to a second engagement feature of theshaft 1640 such that rotation of the control element 1660 relative tothe base 1626 causes translation of the shaft 1640 relative the base1626 (and translation of the laser catheter 1612 within the lumen of thecatheter 1616 and within the balloon). For example and as shown in theFigures, the first engagement feature may be a first threaded surface1694 within the control element 1660, and the second engagement featuremay be a second threaded surface 1696 formed on the arcuate sidesurfaces 1644 of the shaft 1640. Stated differently, the shaft 1640 mayinclude a second, interrupted threaded surface that extends from theopening 1654 in the frame 1630 to engage the first threaded surface 1694of the control element 1660. In any case, rotation of the controlelement 1660 and the first threaded surface 1694, together with theshaft 1640 being rotatably fixed within the frame 1630, causestranslation of the second threaded surface 1696 and the shaft 1640relative to the frame 1630 (and translation of the laser catheter 1612within the lumen of the catheter 1616 and within the balloon).

As discussed above with respect to FIG. 5, the present disclosurediscusses using a laser catheter to ablate at least a portion of thevascular occlusion in the vessel of the subject prior to using theballoon catheter to disrupt the remaining portion of the vascularocclusion. FIGS. 20-21F are included to illustrate the formation of avascular occlusion within the vasculature of a subject. Referring toFIG. 20, there is depicted a cross-sectional view of a healthy arterialwall 2000 taken along a direction perpendicular to the longitudinal axisof the arterial wall. A healthy arterial wall 2000, or vascular wall,typically includes an outer layer referred to as the “adventitia” or“adventicia” which is shown in FIG. 20 as layer 2020. There may beadditional layers, such as layer 2010 of the arterial wall 2000, on theoutside of the adventitia. A healthy arterial wall 2000 also includes amiddle or central layer referred to as the media 2030. The media 2030 islocated radially inward of and adjacent to the inner portion of theadventitia 2020. The media 2030 has a layers of smooth muscle cells andlayers of elastin fiber that allows the artery to expand and contract. Ahealthy arterial wall 2000 also includes an inner layer referred to asthe intima 2040. The intima 2040 is located radially inward of andadjacent to the media 2030. A healthy arterial wall 2000 also includesan endothelium layer 2050, which is located on the inner most surface ofthe intima 2040 and creates the boundary for the passageway (or innerlumen) 2060.

As mentioned above, the media 2030 is located radially inward of andadjacent to the inner portion of the adventitia 2020. Specifically, anexternal elastic membrane, commonly referred to as the external elasticlamina, 2035 separates the media 2030 from the adventitia 2020. As alsomentioned above, the intima 2040 is located radially inward of andadjacent to the inner portion of the media 2030. An internal elasticmembrane 2025, commonly referred to as the internal elastic lamina,separates the intima 2040 from the media 2030.

Referring to FIG. 20A, there is depicted a smaller version of thestructure of the healthy arterial wall 2000 depicted in FIG. 20. Also,FIG. 21A is a longitudinal-sectional view of the healthy arterial wall2000 taken along a direction parallel to the longitudinal axis of thearterial wall. Specifically, FIG. 21A is a longitudinal-sectional viewof the structure of the healthy arterial wall 2000 taken along line B-Bof FIG. 20A.

Referring to FIG. 21B, over time, fat and/or lipids 2070′ may start tocollect and/or deposit in the intima 2040′ of the arterial wall 2000′ asa result of buildup of fat and lipids in the blood. This disease processis commonly referred to as atherosclerosis and occurs in the arteries ofthe body including the coronary and peripheral arteries. It is thiscollection of fat and/or lipids 2070′ in the intima 2040′ that will leadto the formation of a vascular occlusion that can reduce or completelyobstruct blood flow in the passageway 2060′. Overtime this buildup offat and lipids 2070′ becomes a heterogeneous mix 2065″ (commonlyreferred to as plaque) of many constituents including but not limited tofats, lipids, fibrin, fibro-calcific plaque, calcium crystals, thrombus,etc. For example, a portion of the fat and/or lipids 2070′ may turn intoplaque 2065″ and even become calcified, which is depicted as 2055″ inFIG. 21C. As the fat and/or lipids 2070″ collect, turn into plaque 2065″and/or become calcified 2055″, the intima 2040″ starts to inflame andexpand, thereby decreasing the cross-sectional area of the passageway2060″.

Referring to FIG. 21D, as atherosclerotic disease progresses, and thecondition of the arterial wall 2000′″ is left untreated, the plaque2065′″ continue to collect, and the intima 2040′″ continues to expandand decrease the cross-sectional area of the passageway 2060′″. However,upon the intima 2040′ of the arterial wall 2000′ reaching its limit toexpand further, the intima 2040′ and the endothelium can rupture 2058′and release the plaque contents previously contained in the thickenedlipids and enlarged intima white blood cells into the passageway2060′{hacek over ( )} as depicted in FIG. 21E. Platelets and fibrincollect within the passageway 2060{hacek over ( )} of the arterial wall2000{hacek over ( )} to try and repair the rupture, and in doing so forman occlusion 2080{hacek over ( )}, which may have calcified portions2085{hacek over ( )}, as depicted in FIG. 21F. This figure alsoillustrates that formation of the occlusion 2080{hacek over ( )} furtherdecreases the size of the passageway 2060{hacek over ( )} and in someinstances fully obstructs flow.

Referring to FIG. 21D and FIG. 21G, a laser catheter 1020 may be used todebunk or remove plaque buildup contained behind the intima 2065′″ orwithin the occlusion 2080{hacek over ( )}′ or a portion thereof from thepassageway of the arterial wall 2000{hacek over ( )}″. After debunkingthe plaque buildup or the occlusive disease, the catheter of the presentdisclosure may be used to treat the remaining portion of the plaquebuildup 2065′″ or the occlusion 2080{hacek over ( )}′, particularly bydisrupting the calcified portions 2085{hacek over ( )}″ as depicted inFIG. 21H by use of laser-induced pressure waves as described previously,thereby leaving the treated arterial wall 2000{hacek over ( )}″ in acondition as depicted in FIG. 21I. FIG. 21I illustrates the arterialwall 2000{hacek over ( )}″ with an enlarged passageway 2060{hacek over ()}″, the majority of the plaque 2065′″ or occlusion 2080{hacek over ()}″ removed, and the calcification of the remaining portion of theocclusion, along with the calcification of the intima 2040{hacek over ()}″, fractured or modified making it more amenable to dilation at loweratmospheric pressures. FIGS. 20A and 21A-21I use similar numeric values,but the different figures include different indicators, such as ′ and{hacek over ( )} and combinations thereof, for the numeric values due tothe changes occurring within the arterial wall as the occlusion isformed and treated, which is progressively illustrated from one figureto the next. For purposes of brevity, certain layers of the arterialwall 2000 are omitted from the discussion of particular figures, andnumeric values of certain items of the arterial wall 2000 are omittedfrom the particular figures. Nevertheless, one should consider thelayers of the arterial wall 2000, and the formations therein, to havethe same numeric values even if omitted from FIGS. 20A and 21A-21I.

Referring to FIG. 22, there is a method 2200 of removing plaque buildupor occlusive disease by performing an atherectomy procedure and treatingthe remainder of the occlusion within the intima with the catheter ofthe present disclosure. This method 2200 may be used to treat coronaryarteries and/or peripheral arteries including but not limited toarteries of the vasculature of the legs, the renal arteries, subclavianarteries, etc. The method 2200 in FIG. 22 includes locating a vascularobstruction or restriction in the vessel of a subject at step 2210. Thenext step 2215, which is optional, includes locating a guidewire at theocclusion and/or inserting a guidewire through the occlusion or throughthe passageway past the occlusion. Step 2220 includes performing anatherectomy procedure to remove the plaque or occlusion or a portionthereof. One type of atherectomy device is an ablation catheter, such asa laser ablation catheter, which is capable of ablating at least aportion of the vascular occlusion. Other types of ablation cathetersinclude radiofrequency ablation catheters, microwave ablation catheters,and cryoablation catheters. Atherectomy devices other than ablationcatheters, such as mechanical atherectomy devices, may also be used toremove the occlusion.

After the occlusion (or a portion thereof) is removed from thevasculature, step 2225 may then be performed. Step 2225 includespositioning a balloon catheter of the present disclosure adjacent thevascular occlusion. For example, if a clinician uses a catheter 100,800, 1000 or any other catheter described herein, which have a guidewirelumen, the catheter(s) may be slid over the guidewire and into thevasculature such that the balloon catheter, which is coupled to thecatheter(s), is positioned adjacent to the vascular obstruction orrestriction (or remainder thereof). At step 2230, the emitters includedwith the laser catheter are positioned (and subsequently re-positioned)at any desired location along the length of the balloon. The method 2200also includes step 2240, which comprises inflating the balloon catheterby delivering the liquid medium (for example, contrast medium) from theinner lumen of the catheter through one or more liquid medium ports andinto the balloon catheter 1050. Additionally or alternatively, themethod may include step 2245, which includes inserting additional lightabsorbing material into the balloon catheter in the general path of thelaser light to be emitted. In some cases, the method 2200 includes thestep 2250 of activating at least one energy source coupled to at leastone emitter enclosed within the balloon catheter to emit and send pulsesof laser light energy into and/or to react with the liquid medium toproduce propagating laser-induced pressure waves and disrupt a remainingportion of the vascular occlusion. Disrupting the remaining portion ofthe vascular occlusion, particularly any calcified portions within thevascular occlusion, produces cracks in the calcified portions and/orreduces the size of the calcified portions because the pressure wavesdisrupt the calcified portions, thereby cracking the calcified portionsand/or fragmenting the size of the calcified particles such that thecontiguous area is reduced. In some cases, the method 2200 includes thestep 2260 of activating at least one energy source coupled to at leastone emitter enclosed within the balloon catheter to emit and send pulsesof laser light energy into and/or to react with the liquid medium toproduce propagating laser-induced pressure waves to deliver atherapeutic agent to a remaining portion of the vascular occlusionand/or the vascular tissue near the occlusion.

One of the benefits of the present disclosure is that the catheter andballoon catheter depicted in FIG. 21H may optionally include areflective element, such as the pressure-wave reflective element 880depicted over the balloon 850 of FIG. 8 above. The pressure-wavereflective element 880, or the alternatives illustrated in FIGS.15A-15F, may reduce or prevent the formation of vapor bubbles on theexterior of the pressure-wave reflective element and/or the balloonand/or reinforces the balloon such as to minimize or prevent balloonexpansion. Reinforcing the balloon and/or reducing or preventing theformation of vapor bubbles on the exterior of the pressure-wavereflective element reduces or prevents the balloon catheter fromdilating the arterial wall while simultaneously allowing the pressurewave to penetrate the arterial wall and disrupt calcified portions inthe occlusion and/or intima. That is, incorporating a pressure-wavereflective element, reinforcing the balloon and/or reducing orpreventing the formation of vapor bubbles on the exterior of thepressure-wave reflective element potentially inhibits displacement ofthe soft tissue within the arterial wall and potential delamination ofthe layers of the arterial wall.

Although the method illustrated in FIG. 22 depicts steps 2210 through2270 of method 2200 as being performed serially, any or all of the stepswithin the method 2200 may in any order and/or in parallel with any ofthe other steps. For example, activating an emitter to disrupt a portionof a vascular occlusion and/or to deliver a therapeutic agent can beperformed in any sequence, if at all, as part of the method 2200. Forexample, step 2250 could be performed without performing step 2260, step2260 could be performed without performing step 2250, step 2250 could beperformed serially while performing step 2260, such that step 2250 isperformed firstly and step 2260 is performed secondly, step 2260 couldbe performed serially while performing step 2250, such that step 2260 isperformed firstly and step 2250 is performed secondly, or steps 2250 and2260 could be performed in parallel. Upon completing step 2250 and/orstep 2260, the balloon catheter can optionally be repositioned withinthe vasculature and adjacent another portion thereof. Similarly, uponcompleting step 2250 and/or step 2260, the emitter(s) can optionally berepositioned within the balloon. The balloon can be repositioned withinthe vasculature and/or the emitter(s) can be repositioned within theballoon. The method 2200 also includes ending the procedure when thedesired therapeutic outcome is obtained, or repeating any of steps 2210through 2260 as may be necessary to treat a subject having a vascularobstruction or restriction. Furthermore, if step 2260 is not performedin the method 2200, a drug eluting (coated) balloon (DEB or DCB)catheter may be used to deliver drugs to the remnants of the vascularocclusion. Disrupting the remaining portion of the vascular occlusionwith the laser-induced pressure waves prior to utilizing a DEB mayincrease the effectiveness of the drugs being applied to the vascularocclusion because the laser-induced pressure waves disrupt calciumformed in the intima layer, as well as media layer of the vascularwall(s), thereby creating a pathway for the drug to enter the intima andmedia layers of the vasculature and/or vascular occlusion.

The present disclosure also contemplates using the laser-induced balloonassembly with conventional angioplasty balloons, as well as with DEBs.For example, a surgical procedure may include performing an atherectomywith a laser catheter, using the laser-induced balloon assembly to treatthe calcified portions of the vasculature as set forth in FIG. 22 above,and then inserting an angioplasty balloon into the vasculature adjacentthe relevant portion of the vasculature and expanding the angioplastyballoon to dilate the relevant portion of the vasculature.

As discussed above, the laser-induced pressure waves created by thecatheter of the present disclosure not only disrupt occlusion and/orcalcium in the intima layer, the laser-induced pressure waves created bythe catheter of the present disclosure can also disrupt calcification ofthe media layer within the vascular wall(s). That is, the laser-inducedpressure waves may be used to fracture or modify calcified mediaregardless of whether the vasculature includes an occlusion. Forexample, patients with medial artery calcification, which is also knownas Mönckeberg's sclerosis, could potentially benefit from being treatedwith the catheter of the present disclosure.

Referring to FIG. 23A, there is depicted a healthy arterial wall 2300similar to the arterial wall depicted in FIG. 21A. For example,reference numerals 2010, 2020, 2030, 2040, 2050 and 2060 of FIG. 21Acorrespond to reference numerals 2310, 2320, 2330, 2340, 2350 and 2360of FIG. 23A. That is, reference numerals 2310 and 2320 are the externa,reference numeral 2330 is the media, reference numeral 2340 is theintima, reference numeral 2350 is the endothelium, and reference numeral2360 is the passageway.

Referring to FIG. 23B, there is depicted is a cross-sectional view of anarterial wall 2300′ that includes calcium deposits 2370 formed in themedia 2330. The calcium deposits begin as crystal aggregates andtypically aggregate along the elastin fibrin layers within the media. AsMönckeberg's sclerosis (commonly referred to as medial calcification)progresses, multiple layers of calcium can form that involve up to thefull circumference of the vessel. The calcium can also extend radiallyinto the adventitia and intima layers. Mönckeberg's sclerosis (medialcalcification) is caused by a recruitment of calcium by the smoothmuscle cells and is attributed but not limited to common comorbiditiesfound in patients suffering from vascular disease including diabetics,kidney disease patients and other metabolic or hormonal imbalances. Themedia 2330 includes smooth muscle cells and elastin fiber, which allowthe artery to expand and contract. Upon formation of calcium deposits2370, however, the artery's ability to expand and contract is reduced.That is, formation of calcium deposits 2370 in the media 2330 reducesthe compliance of the artery 2300′, which in turn potentially reducesthe amount of blood flow through such arteries and can potentiallynegatively affect other health conditions, such as diabetes. Thiscondition can occur with atherosclerotic disease as described previouslyor be an isolated condition without the narrowing of the lumen of theartery.

The catheter of the present disclosure is able to create laser-inducedpressure waves, which fracture or disrupt the calcium deposits 2370 inthe media 2330 of the arterial wall 2300″ as shown in FIG. 23C, therebyincreasing the compliance of the arterial wall 2300′″ and blood flowtherethrough. Furthermore, one of the benefits of the present disclosureis that the catheter and balloon catheter depicted in FIG. 23C, mayoptionally include a reflective element, such as the pressure-wavereflective element 880 depicted over the balloon 850 if FIG. 8 above.The pressure-wave reflective element 880, or the alternativesillustrated in FIGS. 15A-15F, may reduce or prevent the formation ofvapor bubbles on the exterior of the pressure-wave reflective elementand/or the balloon and/or reinforces the balloon such as to minimize orprevent balloon expansion. Reinforcing the balloon and/or reducing orpreventing the formation of vapor bubbles on the exterior of thepressure-wave reflective element reduces or prevents the ballooncatheter from expanding and contracting the arterial wall whilesimultaneously allowing the laser-induced pressure wave to penetrate thearterial wall and hammer calcium deposits in media.

FIGS. 23A-2D use similar numeric values, but the different figuresinclude different indicators, such as ′ and {hacek over ( )} andcombinations thereof, for the numeric values due to the changesoccurring within the arterial wall as the calcium in the media is formedand treated, which is progressively illustrated from one figure to thenext. For purposes of brevity, certain layers of the arterial wall 2300are omitted from the discussion of particular figures, and numericvalues of certain items of the arterial wall 2300 are omitted from theparticular figures. Nevertheless, one should consider the layers of thearterial wall 2300, and the formations therein, to have the same numericvalues even if omitted from FIGS. 23A-23D.

Referring to FIG. 24, there is depicted a method 2400 of using acatheter to generate laser-induced pressure waves to treat the calciumdeposits in the media by disrupting the calcium deposits to increasevasculature compliance, thereby increasing blood flow therethrough. Thismethod 2400 may be used to treat calcium deposits in the media ofcoronary arteries and/or peripheral arteries. The method 2400 in FIG. 24includes locating a calcification in the media within the vasculature ofa subject at step 2410. The next step 2420, which is optional, includeslocating a guidewire at the occlusion and/or inserting a guidewirethrough the occlusion or through the passageway past the portion of thevasculature that includes the calcified portion(s) in the media.

After locating the calcified portion(s) in the media within thevasculature, step 2425 may then be performed. Step 2425 includespositioning a balloon catheter of the present disclosure adjacent thevasculature that includes the calcified portion(s) in the media. Forexample, if a clinician uses a catheter 100, 800, 1000 or any othercatheter described herein, which have a guidewire lumen, the catheter(s)may be slid over the guidewire and into the vasculature such that theballoon catheter, which is coupled to the catheter(s), is positionedadjacent to the vascular obstruction or restriction (or remainderthereof). At step 2430, the emitters included with the laser catheterare positioned (and subsequently re-positioned) at any desired locationalong the length of the balloon. The method 2400 also includes step2440, which comprises inflating the balloon catheter by delivering theliquid medium (for example, contrast medium) from the inner lumen of thecatheter through one or more liquid medium ports and into the ballooncatheter 1050. Additionally or alternatively, the method may includestep 2445, which includes inserting additional light absorbing materialinto the balloon catheter in the general path of the laser light to beemitted. In some cases, the method 2400 includes the step 2450 ofactivating at least one energy source coupled to at least one emitterenclosed within the balloon of the balloon catheter to crack thecalcified portion(s) in the media and/or breaks the calcified portionsinto smaller particles. Disrupting the calcified portion(s) within themedia cracks the calcified portion(s) because the laser-induced pressurewaves are absorbed by the calcified portions. In some cases, the method2400 includes the step 2460 of activating at least one energy sourcecoupled to at least one emitter enclosed within the balloon of theballoon catheter to emit and send pulses of laser light energy intoand/or to react with the liquid medium to produce propagatinglaser-induced pressure waves to deliver a therapeutic agent to throughthe cracks in the calcified portions through the cracks in the calcifiedportions and/or through (or to) potentially.

Referring again to step 2450 of method 2400 in FIG. 24, the emission ofpropagating laser-induced pressure waves from the balloon catheter intothe calcified portions in the media disrupts the calcified portion(s) inthe media. Disrupting the calcified portion(s) within the media cracksthe calcified portion and/or reduces the size of the calcifiedportion(s) because the laser-induced pressure waves are absorbed by thecalcified portion(s), thereby increasing the arterial wall's compliance,which in turn leads to improved blood flow and positive implications forother health conditions.

EXAMPLES Example 1

Vascular Testing: Improved Arterial Wall Compliance

An example of the benefit of using a laser-induced balloon catheter ofthe present disclosure is as follows. Using optical coherencetomography, a section of an artery from a cadaver, namely thesuperficial femoral artery to the posterior tibial artery, havingcalcium segments in both the intima and media was identified. A 5.0 mmballoon catheter was inserted into the artery and inflated to 1 atmwhile the balloon was located at the relevant segment. Upon inflation to1 atm, the balloon had a diameter of about 4.90 mm at its largest pointof inflation within the artery and about 3.35 mm over a length of 13.3mm at its minimum point of inflation, which occurred at the location ofthe occlusion. Moreover, the artery's minimum lumen area (MLA) was about8.93 mm², and the diameter stenosis (the minimum lumen diameter dividedby the maximum lumen diameter) was about 27.4%. A Spectranetics 2.0 mmover-the-wire (OTW) Turbo-Elite™ laser atherectomy catheter was insertedinto the balloon which was filled to 1 atm with a solution comprising50% saline solution and 50% contrast media. The Turbo-Elite™ laseratherectomy catheter produced pulsed laser light at 1 Hz and produced 50mJ of energy per pulse for about 40 to 50 pulses while translatinginside the fluid filled balloon. After firing the laser catheter withinthe fluid filled balloon, the balloon inflated at 1 atm to a diameter ofabout 5.3 mm at one of its largest points of inflation within the arteryand about 4.97 mm over a length of 9.33 mm at its minimum point ofinflation. Moreover, the artery's minimum lumen area (MLA) was about19.54 mm², and the diameter stenosis (the minimum lumen diameter dividedby the maximum lumen diameter) was about 10.5%. Accordingly, using theminimum lumen area (MLA) was increased about 131%, namely from about8.93 mm² to about 19.54 mm², and the diameter of the artery at theocclusion increased about 52%, namely from about 3.35 mm to about 4.90mm.

Treatment using a laser-induced balloon catheter significantly improvedtissue compliance.

Example 2

Vascular Testing: Improved Arterial Wall Compliance at Reduced InflationPressure

Another example of the benefit of using a laser-induced balloon catheterof the present disclosure is as follows. An angioplasty balloon was usedas a control. Using optical coherence tomography, a section of an arteryfrom a cadaver having calcium segments in both the intima and media wasidentified. A 6 mm balloon catheter was inserted into the identifiedsection of the artery and inflated to 1 atm while the balloon waslocated at the relevant arterial segment. Upon inflation to 1 atm, theballoon had a mean diameter of about 1.92 mm and a cross sectional areaof about 2.91 mm². The balloon catheter was then inflated to 6 atm,which is a “nominal” pressure for treating a stenosed artery. Uponreaching this inflation pressure, the balloon had a mean diameter of3.50 mm and covered a cross sectional area of the artery equating toabout 9.67 mm².

The same 6 mm balloon was inserted into a different section of an arteryfrom a cadaver having calcium segments in both the intima and media wasidentified. A similarly sized angioplasty balloon catheter was theninserted into a more distal segment of the same calcified artery andinflated to 1 atm, while the balloon was located at the relevantarterial segment. Upon inflation to 1 atm, the balloon had a meandiameter of about 1.92 mm and an area of about 2.90 mm², very similar tothe previously treated segment. The balloon catheter was then inflatedto 1 atm, and upon reaching this inflation pressure, the balloon had amean diameter of 3.5 mm and covered a cross sectional area of the arteryequating to about 9.67 mm². The angioplasty balloon catheter was thenremoved from the artery. Subsequently, a Spectranetics 2.0 mmover-the-wire (OTW) Turbo-Elite™ laser atherectomy catheter was insertedinto the balloon. The balloon was filled to 1 atm with a solutioncomprising 50% saline solution and 50% contrast media. The Turbo-Elite™laser atherectomy catheter produced pulsed laser light at 1 Hz andproduced 30 mJ of energy per pulse for 15 pulses while translatinginside the fluid filled balloon. The laser atherectomy catheter wasremoved from the balloon. After firing the laser catheter within thefluid filled balloon, the fluid filled balloon was removed from thearterial section, and the previously inserted angioplasty ballooncatheter was reinserted and inflated. Specifically, the balloon catheterwas inflated to a pressure of 4 atm. At this pressure the diameter ofthe balloon expanded to about 3.23 mm and had a cross sectional area ofabout 8.34 mm². All measurements were taken using optical coherencetomography. After treatment with the laser-induced pressure wave, theballoon expanded within the calcified artery, and the fluid filledangioplasty balloon was able to expand to a similar diameter within anartery having calcified media but required less pressure to do so-aboutone-third the amount of inflation pressure.

Treatment using a laser-induced pressure wave inside a balloonsignificantly reduced the amount of pressure required to dilate anartery with a calcified media.

The present disclosure, in various aspects, embodiments, andconfigurations, includes components, methods, processes, systems and/orapparatus substantially as depicted and described herein, includingvarious aspects, embodiments, configurations, sub combinations, andsubsets thereof. Those of skill in the art will understand how to makeand use the various aspects, aspects, embodiments, and configurations,after understanding the present disclosure. The present disclosure, invarious aspects, embodiments, and configurations, includes providingdevices and processes in the absence of items not depicted and/ordescribed herein or in various aspects, embodiments, and configurationshereof, including in the absence of such items as may have been used inprevious devices or processes, for example, for improving performance,achieving ease and\or reducing cost of implementation.

The foregoing discussion of the disclosure has been presented forpurposes of illustration and description. The foregoing is not intendedto limit the disclosure to the form or forms disclosed herein. In theforegoing Detailed Description for example, various features of thedisclosure are grouped together in one or more, aspects, embodiments,and configurations for the purpose of streamlining the disclosure. Thefeatures of the aspects, embodiments, and configurations of thedisclosure may be combined in alternate aspects, embodiments, andconfigurations other than those discussed above. This method ofdisclosure is not to be interpreted as reflecting an intention that theclaimed disclosure requires more features than are expressly recited ineach claim. Rather, as the following claims reflect, inventive aspectslie in less than all features of a single foregoing disclosed aspects,embodiments, and configurations. Thus, the following claims are herebyincorporated into this Detailed Description, with each claim standing onits own as a separate preferred embodiment of the disclosure.

Moreover, though the description of the disclosure has includeddescription of one or more aspects, embodiments, or configurations andcertain variations and modifications, other variations, combinations,and modifications are within the scope of the disclosure, for example,as may be within the skill and knowledge of those in the art, afterunderstanding the present disclosure. It is intended to obtain rightswhich include alternative aspects, embodiments, and configurations tothe extent permitted, including alternate, interchangeable and/orequivalent structures, functions, ranges or steps to those claimed,whether or not such alternate, interchangeable and/or equivalentstructures, functions, ranges or steps are disclosed herein, and withoutintending to publicly dedicate any patentable subject matter.

What is claimed is:
 1. A method for improving the compliance of a bloodvessel within a subject, the method comprising: locating a calcifiedportion in the media of the blood vessel of the subject; positioning acatheter within the blood vessel, the catheter comprising: a tube havinga lumen, a proximal end and a distal end; one or more emitters arrangedaround or adjacent to the lumen, wherein the emitters have respectivedistal ends disposed adjacent the distal end of the tube; a ballooncircumferentially arranged around a portion of the distal end of thetube; and one or more liquid medium ports disposed about the catheterand within the balloon; positioning the balloon adjacent the calcifiedportion in the media; inflating the balloon by delivering a liquidmedium through an inner lumen of the tube and out one or more liquidmedium ports into the balloon until a desired inflation pressure isobtained; and emitting one or more pulses of light energy from thedistal end of the emitters, wherein the one or more pulses of lightenergy reacts with the liquid medium and generates a plurality ofpropagating laser-induced pressure waves that disrupt the calcifiedportion of media, thereby improving the compliance of the blood vessel.2. The method of claim 1, wherein the at one or more pulses of lightenergy comprises a wavelength of between about 300 nanometers to about350 nanometers, at pulse durations between about 100 nanoseconds toabout 150 nanoseconds, and at frequencies between about 1 pulse persecond to about 250 pulses per second.
 3. The method of claim 1, whereinthe liquid medium is any one of iodine-containing contrast medium orgadolinium contrast medium.
 4. The method of claim 1, wherein theinflation pressure obtained by delivering liquid medium into thedilation balloon is between about 0.25 atmospheres and about 5.0atmospheres of pressure.
 5. The method of claim 1, wherein the pluralityof propagating laser-induced pressure waves enhances penetration of oneor more therapeutic agents into the media.
 6. The method of claim 5,wherein the one or more therapeutic agents comprises one or moreoxidation-insensitive drugs in a polymer-free drug preparation.
 7. Themethod of claim 6, wherein the one or more oxidation-insensitive drugsis one or more of taxanes, thalidomide, statins, corticoids, andlipophilic derivatives of corticoids.
 8. The method of claim 5, whereinthe one or more pulses of light energy comprises a wavelength a of about308 nanometers, at pulse durations between about 120 nanoseconds andabout 140 nanoseconds, and at frequencies between about 25 pulses persecond to about 80 pulses per second.
 9. The method of claim 5, whereintotal energy output for the one or more pulses of light energy comprisesenergy between about 30 to about 80 millijoules per millimeter squared(mJ/mm²).
 10. A method for disrupting a calcified portion containedwithin the media of a blood vessel wall of a subject, the methodcomprising: positioning a catheter within the blood vessel of thesubject, the catheter comprising: a tube having a guidewire lumen, aninflation lumen, a proximal end and a distal end; a plurality ofemitters circumferentially arranged around or adjacent to the guidewirelumen, wherein at least a portion of the plurality of emitters comprisesa distal end; a balloon circumferentially arranged around a portion ofthe tube and around at least a portion of the distal end of theemitters; one or more liquid medium ports disposed within the tube andwithin the balloon; and a pressure-wave reflective element disposedadjacent the balloon; positioning the balloon adjacent the calcifiedportion in the media of the blood vessel; inflating the balloon bydelivering a liquid medium through the inflation lumen and out one ormore liquid medium ports into the balloon until a desired inflationpressure is obtained; and emitting at least one pulse of light energyfrom the distal end of the emitters, whereupon the light energy reactswith the liquid medium and generates one or more laser-induced pressurewaves that propagate through the balloon and disrupt the calcifiedportion in the media, wherein the pressure-wave reflective elementreduces formation of vapor bubbles arising from the laser-inducedpressure wave.
 11. The method of claim 10, wherein the pressure-wavereflective element comprises a plurality of openings.
 12. The method ofclaim 11, wherein the plurality of openings are between 10 microns and10 millimeters.
 13. The method of claim 11, wherein a percentage of theopenings within an area of a portion of the pressure-wave reflectiveelement is between 10 percent and 90 percent.
 14. The method of claim11, wherein an area of the pressure-wave reflective element comprisesthe openings and a structural mass, wherein a ratio of the openings tothe structural mass within the area is between 10:1 and 1:10.
 15. Themethod of claim 11, wherein the plurality of openings comprise at leastone of the following shapes: circle; oval; triangle; square; rectangle;polygon; diamond; pentagon; hexagon; heptagon; octagon; nonagon; anddecagon.
 16. The method of claim 15 further comprising the step ofre-positioning the balloon such that the balloon is adjacent anotherportion of the obstruction or restriction.
 17. The method of claim 16further comprising the step of moving the plurality of emitters withinthe balloon.
 18. The method of claim 17, wherein the within theplurality of emitters is re-positioned within the pressure-wavereflective element.
 19. The method of claim 11 further comprising thestep of re-positioning the plurality of emitters within the balloon. 20.The method of claim 11, wherein the within the plurality of emitters isre-positioned within the pressure-wave reflective element.